bluuebunny/crossref_metadata_2025 huggingface dataset:
Checkpoint Inhibitors and the Gut
Authors: Tran Tuan , Tran Nguyen Giang Tien , Ho Vincent
Published: February 2022

Checkpoint inhibitors have revolutionized treatments in modern oncology, including many conditions previously relegated to palliative therapies only. However, emerging recognition of checkpoint inhibitor-related adverse events has complicated the status of checkpoint inhibitor-related therapies. This review article discusses gastrointestinal adverse events as a result of checkpoint inhibitor therapy, as well as limitations of current guidelines, thus providing recommendations for guideline revision and future study direction.
Effect of Carbohydrate-Enriched Drink Compared to Fasting on Hemodynamics in Healthy Volunteers. A Randomized Trial
Authors: Kukliński Jakub , Steckiewicz Karol P. , Piwowarczyk Sebastian P. , Kreczko Mateusz J. , Aszkiełowicz Aleksander , Owczuk Radosław
Published: February 2022

Fasting prior to surgery can cause dehydration and alter hemodynamics. This study aimed to determine the impact of a carbohydrate-enriched drink (NutriciaTM Pre-op®) on selected hemodynamical parameters, measured in a non-invasive manner. We enrolled 100 healthy volunteers and measured their weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), thoracic fluid content (TFC), thoracic fluid index (TFCI), stroke volume (SV), stroke volume variation (SVV), stroke index (SI), cardiac output (CO), cardiac index (CI), heather index (HI), systolic time ration (STR), systemic time ratio index (STRI), systemic vascular resistance (SVR), and systemic vascular resistance index (SVRI) by a Niccomo™ device, implementing the impedance cardiography (ICG) method. Measurements were performed at the beginning of the study, and after 10 h and 12 h. We randomly allocated participants to the control group and the pre-op group. The pre-op group received 400 mL of Nutricia™ preOp®, as suggested in the ERAS guidelines, within 10 h of the study. Student’s t-test or the Mann–Whitney U test were used to compare the two groups, and p < 0.05 was considered significant. We did not observe any changes in hemodynamical parameters, blood pressure, and heart rate between the groups. We have proven that carbohydrate-enriched drink administration did not have a significant impact on the hemodynamical parameters of healthy volunteers.
Is NMDA-Receptor-Mediated Oxidative Stress in Mitochondria of Peripheral Tissues the Essential Factor in the Pathogenesis of Hepatic Encephalopathy?
Authors: Kosenko Elena , Tikhonova Lyudmila , Alilova Gubidat , Montoliu Carmina
Published: February 2022

Background: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of increased ammonia-mediated brain dysfunction caused by impaired hepatic detoxification or when the blood bypasses the liver. Ammonia-activated signal transduction pathways of hyperactivated NMDA receptors (NMDAR) are shown to trigger a cascade of pathological reactions in the brain, leading to oxidative stress. NMDARs outside the brain are widely distributed in peripheral tissues, including the liver, heart, pancreas, and erythrocytes. To determine the contribution of these receptors to ammonia-induced oxidative stress in peripheral tissues, it is relevant to investigate if there are any ammonia-related changes in antioxidant enzymes and free radical formation and whether blockade of NMDARs prevents these changes. Methods: Hyperammonemia was induced in rats by ammonium acetate injection. Oxidative stress was measured as changes in antioxidant enzyme activities and O2•− and H2O2 production by mitochondria isolated from the tissues and cells mentioned above. The effects of the NMDAR antagonist MK-801 on oxidative stress markers and on tissue ammonia levels were evaluated. Results: Increased ammonia levels in erythrocytes and mitochondria isolated from the liver, pancreas, and heart of hyperammonemic rats are shown to cause tissue-specific oxidative stress, which is prevented completely (or partially in erythrocyte) by MK-801. Conclusions: These results support the view that the pathogenesis of HE is multifactorial and that ammonia-induced multiorgan oxidative stress-mediated by activation of NMDAR is an integral part of the disease and, therefore, the toxic effects of ammonia in HE may be more global than initially expected.
Current Controversies and Challenges on BRAF V600K-Mutant Cutaneous Melanoma
Authors: Nepote Alessandro , Avallone Gianluca , Ribero Simone , Cavallo Francesco , Roccuzzo Gabriele , Mastorino Luca , Conforti Claudio , Paruzzo Luca , Poletto Stefano , Carnevale Schianca Fabrizio , Quaglino Pietro , Aglietta Massimo
Published: February 2022

About 50% of melanomas harbour a BRAF mutation. Of these 50%, 10% have a V600K mutation. Although it is the second most common driver mutation after V600E, no specific studies have been conducted to identify a clinical and therapeutic gold standard for this patient subgroup. We analysed articles, including registrative clinical trials, to identify common clinical and biological traits of the V600K melanoma population, including different adopted therapeutic strategies. Melanoma V600K seems to be more frequent in Caucasian, male and elderly populations with a history of chronic sun damage and exposure. Prognosis is poor and no specific prognostic factor has been identified. Recent findings have underlined how melanoma V600K seems to be less dependent on the ERK/MAPK pathway, with a higher expression of PI3KB and a strong inhibition of multiple antiapoptotic pathways. Both target therapy with BRAF inhibitors + MEK inhibitors and immunotherapy with anti-checkpoint blockades are effective in melanoma V600K, although no sufficient evidence can currently support a formal recommendation for first line treatment choice in IIIC unresectable/IV stage patients. Still, melanoma V600K represents an unmet medical need and a marker of poor prognosis for cutaneous melanoma.
How to Choose the Biologic Therapy in a Bio-naïve Patient with Inflammatory Bowel Disease
Authors: Laredo Viviana , Gargallo-Puyuelo Carla J. , Gomollón Fernando
Published: February 2022

The availability of biologic therapies in inflammatory bowel disease (IBD) is increasing significantly. This represents more options to treat patients, but also more difficulties in choosing the therapies, especially in the context of bio-naïve patients. Most evidence of safety and efficacy came from clinical trials comparing biologics with placebo, with a lack of head-to-head studies. Network meta-analysis of biologics and real-world studies have been developed to solve this problem. Despite the results of these studies, there are also other important factors to consider before choosing the biologic, such as patient preferences, comorbidities, genetics, and inflammatory markers. Given that resources are limited, another important aspect is the cost of biologic therapy, since biosimilars are widely available and have been demonstrated to be effective with a significant decrease in costs. In this review, we summarize the evidence comparing biologic therapy in both Crohn´s disease (CD) and ulcerative colitis (UC) in different clinical situations. We also briefly synthesize the evidence related to predictors of biologic response, as well as the biologic use in extraintestinal manifestations and the importance of the drug-related costs.
Actin Filament in the First Cell Cycle Contributes to the Determination of the Anteroposterior Axis in Ascidian Development
Authors: Goto Toshiyuki , Torii Shuhei , Kondo Aoi , Kanda Kazumasa , Kawakami Junji , Kataoka Yosky , Nishikata Takahito
Published: February 2022

In many animal species, the body axis is determined by the relocalization of maternal determinants, organelles, or unique cell populations in a cytoskeleton-dependent manner. In the ascidian first cell cycle, the myoplasm, including mitochondria, endoplasmic reticulum (ER), and maternal mRNAs, move to the future posterior side concomitantly (called ooplasmic segregation or cytoplasmic and cortical reorganization). This translocation consists of first and second phases depending on the actin and microtubule, respectively. However, the transition from first to second phase, that is, translocation of myoplasmic components from microfilaments to microtubules, has been poorly investigated. In this study, we analyzed the relationship between these cytoskeletons and myoplasmic components during the first cell cycle and their role in morphogenesis by inhibitor experiments. Owing to our improved visualization techniques, there was unexpected F-actin accumulation at the vegetal pole during this transition period. When this F-actin was depolymerized, the microtubule structure was strongly affected, the myoplasmic components, including maternal mRNA, were mislocalized, and the anteroposterior axis formation was disordered. These results suggested the importance of F-actin during the first cell cycle and the existence of interactions between microfilaments and microtubules, implying the enigmatic mechanism of ooplasmic segregation. Solving this mystery leads us to an improved understanding of ascidian early development.
Low-Modulus PMMA Has the Potential to Reduce Stresses on Endplates after Cement Discoplasty
Authors: Lewin Susanne , Försth Peter , Persson Cecilia
Published: February 2022

Cement discoplasty has been developed to treat patients with advanced intervertebral disc degeneration. In discoplasty, poly(methylmethacrylate) (PMMA) bone cement is injected into the disc, leading to reduced pain and certain spinal alignment correction. Standard PMMA-cements have much higher elastic modulus than the surrounding vertebral bone, which may lead to a propensity for adjacent fractures. A PMMA-cement with lower modulus might be biomechanically beneficial. In this study, PMMA-cements with lower modulus were obtained using previously established methods. A commercial PMMA-cement (V-steady®, G21 srl) was used as control, and as base cement. The low-modulus PMMA-cements were modified by 12 vol% (LA12), 16 vol% (LA16) and 20 vol% (LA20) linoleic acid (LA). After storage in 37 °C PBS from 24 h up to 8 weeks, specimens were tested in compression to obtain the material properties. A lower E-modulus was obtained with increasing amount of LA. However, with storage time, the E-modulus increased. Standard and low-modulus PMMA discoplasty were compared in a previously developed and validated computational lumbar spine model. All discoplasty models showed the same trend, namely a substantial reduction in range of motion (ROM), compared to the healthy model. The V-steady model had the largest ROM-reduction (77%), and the LA20 model had the smallest (45%). The average stress at the endplate was higher for all discoplasty models than for the healthy model, but the stresses were reduced for cements with higher amounts of LA. The study indicates that low-modulus PMMA is promising for discoplasty from a mechanical viewpoint. However, validation experiments are needed, and the clinical setting needs to be further considered.
Drop Jumping on Sand Is Characterized by Lower Power, Higher Rate of Force Development and Larger Knee Joint Range of Motion
Authors: Giatsis George , Panoutsakopoulos Vassilios , Kollias Iraklis A.
Published: February 2022

Plyometric training on sand is suggested to result in advanced performance in vertical jumping. However, limited information exists concerning the biomechanics of drop jumps (DJ) on sand. The purpose of the study was to compare the biomechanical parameters of DJs executed on rigid (RIGID) and sand (SAND) surface. Sixteen high level male beach-volleyball players executed DJ from 40 cm on RIGID and SAND. Force- and video-recordings were analyzed to extract the kinetic and kinematic parameters of the DJ. Results of paired-samples t-tests revealed that DJ on SAND had significantly (p < 0.05) lower jumping height, peak vertical ground reaction force, power, peak leg stiffness and peak ankle flexion angular velocity than RIGID. In addition, DJ on SAND was characterized by significantly (p < 0.05) larger rate of force development and knee joint flexion in the downward phase. No differences (p > 0.05) were observed for the temporal parameters. The compliance of SAND decreases the efficiency of the mechanisms involved in the optimization of DJ performance. Nevertheless, SAND comprises an exercise surface with less loading during the eccentric phase of the DJ, thus it can be considered as a surface that can offer injury prevention under demands for large energy expenditure.
CondenseNeXtV2: Light-Weight Modern Image Classifier Utilizing Self-Querying Augmentation Policies
Authors: Kalgaonkar Priyank , El-Sharkawy Mohamed
Published: February 2022

Artificial Intelligence (AI) combines computer science and robust datasets to mimic natural intelligence demonstrated by human beings to aid in problem-solving and decision-making involving consciousness up to a certain extent. From Apple’s virtual personal assistant, Siri, to Tesla’s self-driving cars, research and development in the field of AI is progressing rapidly along with privacy concerns surrounding the usage and storage of user data on external servers which has further fueled the need of modern ultra-efficient AI networks and algorithms. The scope of the work presented within this paper focuses on introducing a modern image classifier which is a light-weight and ultra-efficient CNN intended to be deployed on local embedded systems, also known as edge devices, for general-purpose usage. This work is an extension of the award-winning paper entitled ‘CondenseNeXt: An Ultra-Efficient Deep Neural Network for Embedded Systems’ published for the 2021 IEEE 11th Annual Computing and Communication Workshop and Conference (CCWC). The proposed neural network dubbed CondenseNeXtV2 utilizes a new self-querying augmentation policy technique on the target dataset along with adaption to the latest version of PyTorch framework and activation functions resulting in improved efficiency in image classification computation and accuracy. Finally, we deploy the trained weights of CondenseNeXtV2 on NXP BlueBox which is an edge device designed to serve as a development platform for self-driving cars, and conclusions will be extrapolated accordingly.
Fine Identification and Classification of a Novel Beneficial Talaromyces Fungal Species from Masson Pine Rhizosphere Soil
Authors: Sun Xiao-Rui , Xu Ming-Ye , Kong Wei-Liang , Wu Fei , Zhang Yu , Xie Xing-Li , Li De-Wei , Wu Xiao-Qin
Published: February 2022

Rhizosphere fungi have the beneficial functions of promoting plant growth and protecting plants from pests and pathogens. In our preliminary study, rhizosphere fungus JP-NJ4 was obtained from the soil rhizosphere of Pinus massoniana and selected for further analyses to confirm its functions of phosphate solubilization and plant growth promotion. In order to comprehensively investigate the function of this strain, it is necessary to ascertain its taxonomic position. With the help of genealogical concordance phylogenetic species recognition (GCPSR) using five genes/regions (ITS, BenA, CaM, RPB1, and RPB2) as well as macro-morphological and micro-morphological characters, we accurately determined the classification status of strain JP-NJ4. The concatenated phylogenies of five (or four) gene regions and single gene phylogenetic trees (ITS, BenA, CaM, RPB1, and RPB2 genes) all show that strain JP-NJ4 clustered together with Talaromyces brevis and Talaromyces liani, but differ markedly in the genetic distance (in BenA gene) from type strain and multiple collections of T. brevis and T. liani. The morphology of JP-NJ4 largely matches the characteristics of genes Talaromyces, and the rich and specific morphological information provided by its colonies was different from that of T. brevis and T. liani. In addition, strain JP-NJ4 could produce reduced conidiophores consisting of solitary phialides. From molecular and phenotypic data, strain JP-NJ4 was identified as a putative novel Talaromyces fungal species, designated T. nanjingensis.
Ion Channel Involvement in Tumor Drug Resistance
Authors: Altamura Concetta , Gavazzo Paola , Pusch Michael , Desaphy Jean-François
Published: February 2022

Over 90% of deaths in cancer patients are attributed to tumor drug resistance. Resistance to therapeutic agents can be due to an innate property of cancer cells or can be acquired during chemotherapy. In recent years, it has become increasingly clear that regulation of membrane ion channels is an important mechanism in the development of chemoresistance. Here, we review the contribution of ion channels in drug resistance of various types of cancers, evaluating their potential in clinical management. Several molecular mechanisms have been proposed, including evasion of apoptosis, cell cycle arrest, decreased drug accumulation in cancer cells, and activation of alternative escape pathways such as autophagy. Each of these mechanisms leads to a reduction of the therapeutic efficacy of administered drugs, causing more difficulty in cancer treatment. Thus, targeting ion channels might represent a good option for adjuvant therapies in order to counteract chemoresistance development.
Systemic Periodontal Risk Score Using an Innovative Machine Learning Strategy: An Observational Study
Authors: Monsarrat Paul , Bernard David , Marty Mathieu , Cecchin-Albertoni Chiara , Doumard Emmanuel , Gez Laure , Aligon Julien , Vergnes Jean-Noël , Casteilla Louis , Kemoun Philippe
Published: February 2022

Early diagnosis is crucial for individuals who are susceptible to tooth-supporting tissue diseases (e.g., periodontitis) that may lead to tooth loss, so as to prevent systemic implications and maintain quality of life. The aim of this study was to propose a personalized explainable machine learning algorithm, solely based on non-invasive predictors that can easily be collected in a clinic, to identify subjects at risk of developing periodontal diseases. To this end, the individual data and periodontal health of 532 subjects was assessed. A machine learning pipeline combining a feature selection step, multilayer perceptron, and SHapley Additive exPlanations (SHAP) explainability, was used to build the algorithm. The prediction scores for healthy periodontium and periodontitis gave final F1-scores of 0.74 and 0.68, respectively, while gingival inflammation was harder to predict (F1-score of 0.32). Age, body mass index, smoking habits, systemic pathologies, diet, alcohol, educational level, and hormonal status were found to be the most contributive variables for periodontal health prediction. The algorithm clearly shows different risk profiles before and after 35 years of age and suggests transition ages in the predisposition to developing gingival inflammation or periodontitis. This innovative approach to systemic periodontal disease risk profiles, combining both ML and up-to-date explainability algorithms, paves the way for new periodontal health prediction strategies.
Habitat Fragmentation, Connectivity Conservation and Related Key-Concepts: Temporal Trends in Their Recurrences on Web of Science (1960–2020)
Authors: Battisti Corrado , Gallitelli Luca , Scalici Massimiliano , Angelici Francesco M.
Published: February 2022

In this work, we analyzed the temporal trends of nine selected key terms used in the habitat fragmentation arena, quantifying their number (and frequency) of recurrence on Web of Science from 1960 to 2020. The most used key (focal) terms (“stepping stones”, “habitat corridors”, “landscape connectivity”), showed a progressive increase from 1981 to 2020, with “landscape connectivity” showing the highest increase in frequency in the last decade (2011–2020). Among the key secondary terms (recurring < 5%), although “corridors”, “continuity”, and “contiguity” showed a slight growth over the decades, “connectivity conservation” showed the most significant increase. This last landscape-related term recently replaced other local-scale concepts (as “stepping stones” and “corridors”) as a consequence of a change of perspective. Conversely, “ecological network planning”, used in landscape planning and less in conservation biology, showed a comparable fewer recurrence. This gap in recurrences could be due to a bias in our research approach, as Web of Science is a search engine that does not intercept grey literature (as plans and reports) drawn up by Public Agencies which rarely appears in scientific journals.
Decoupling Analysis between Rural Population Change and Rural Construction Land Changes in China
Authors: Zhang Xueru , Wang Jie , Song Wei , Wang Fengfei , Gao Xing , Liu Lei , Dong Kun , Yang Dazhi
Published: February 2022

Developing countries account for about 86.5% of the world’s population and are experiencing rapid urbanization. Globally, the increase in the urban population is generally accompanied by the expansion of the latter and construction lands, as well as the reduction in the rural population and rural construction lands. However, with the rapid development of urbanization in China, the rural population has decreased, while the proportion of rural construction lands has increased, resulting in a significant waste of land resources. In order to quantitatively characterize the degree of deviation between the permanent rural population and rural construction lands based on the 2009–2016 demographic data and land survey data in China, we comprehensively used the decoupling model and the coordination degree model to analyze the temporal change characteristics, spatial distribution law, and the degree of deviation of rural construction land areas and the number of rural permanent residents. Firstly, according to the decoupling model, the type of decoupling between the area of rural construction lands and the number of rural permanent residents at the national scale was strongly negative. Secondly, according to the coordination degree model, the coordination type between rural construction land areas and the rural resident population was uncoordinated; at the provincial scale, the coordination system involved one city and one district (Beijing and the Tibet Autonomous Region) and the basic coordination of two cities (Tianjin and Shanghai). Xinjiang and Qinghai belonged to the reconcilable type, and the other 25 provinces belonged to the uncoordinated type. Finally, according to the comprehensive measurement model, the number of rural permanent residents and rural construction lands showed two types of decoupling: highly strong negative decoupling incoordination and moderately and weakly strong negative decoupling incoordination.
Influential Factors and Geographical Differences in the Redevelopment Willingness of Urban Villagers: A Case Study of Guangzhou, China
Authors: Zhang Lizheng , Ye Yumin , Wang Jiejing
Published: February 2022

As a crucial part of China’s development strategy, the redevelopment of urban villages and the redevelopment willingness of villagers have attracted considerable scholarly interest. However, the literature to date has neglected the effect of the geographical location of urban villages on the redevelopment willingness of villagers. The purpose of this study is to examine the influential factors of the redevelopment willingness of urban villagers, especially with regard to geographical differences and their effects. Based on prospect theory and 1083 questionnaires administered in 45 selected urban villages in Guangzhou, we use the ordinal logistic regression model to explore the influential factors behind villagers’ redevelopment willingness in inner villages (<15 km from the city center), urban fringe villages (15–40 km from the city center), and suburban villages (>40 km from the city center). The results show that in inner villages the confirmation of residential land rights can significantly increase redevelopment willingness, but in urban fringe villages the number of stories in dwelling houses significantly decreases the willingness. Further, a high level of villagers’ trust in the government, market enterprises, and the village collective each has a significant positive impact on the redevelopment willingness of villagers in urban fringe villages. However, only trust in the government and market enterprises have significant positive impacts on redevelopment willingness in the inner villages and only trust in the village collective is significant in this regard in suburban villages. The effects of geographical differences imply that China’s redevelopment policy should be applied in a differentiated way based on the geographical locations of urban villages.
In Silico Molecular Characterization of Human TMPRSS2 Protease Polymorphic Variants and Associated SARS-CoV-2 Susceptibility
Authors: Salleh Mohd Zulkifli , Deris Zakuan Zainy
Published: February 2022

The 2019 coronavirus disease (COVID-19) pandemic continues to challenge health care systems worldwide. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the cause of global pandemic. Type 2 transmembrane serine protease (TMPRSS2) is important in the cell entry and spread of SARS-CoV-2 and plays a crucial role in the proteolytic cleavage of SARS-CoV-2 spike (S) glycoprotein. Here, using reported structural data, we analyzed the molecular complex of TMPRSS2 and the S glycoprotein and further examined intermolecular interactions of natural TMPRSS2 polymorphic variants. We identified several TMPRSS2 variants that could possibly alter host susceptibility to the SARS-CoV-2 infection. Molecular docking analysis revealed that G462D/G462S variants were predicted to be protective variants, whereas Q438E and S339F variants were predicted to increase susceptibility. In addition, we examined intermolecular interactions between TMPRSS2 and its two potential serine protease inhibitors, camostat mesylate and nafamostat. Further, we investigated the effect of TMPRSS2 variants on these interactions. Our structural analysis revealed that G462D, C297S and S460R variants had possibly altered the interactions with the protease inhibitors. Our results identified important TMPRSS2 variations that could be useful to develop high affinity and personalized drugs for treating COVID-19 patients.
AI-Based Pipeline for Classifying Pediatric Medulloblastoma Using Histopathological and Textural Images
Authors: Attallah Omneya , Zaghlool Shaza
Published: February 2022

Pediatric medulloblastomas (MBs) are the most common type of malignant brain tumors in children. They are among the most aggressive types of tumors due to their potential for metastasis. Although this disease was initially considered a single disease, pediatric MBs can be considerably heterogeneous. Current MB classification schemes are heavily reliant on histopathology. However, the classification of MB from histopathological images is a manual process that is expensive, time-consuming, and prone to error. Previous studies have classified MB subtypes using a single feature extraction method that was based on either deep learning or textural analysis. Here, we combine textural analysis with deep learning techniques to improve subtype identification using histopathological images from two medical centers. Three state-of-the-art deep learning models were trained with textural images created from two texture analysis methods in addition to the original histopathological images, enabling the proposed pipeline to benefit from both the spatial and textural information of the images. Using a relatively small number of features, we show that our automated pipeline can yield an increase in the accuracy of classification of pediatric MB compared with previously reported methods. A refined classification of pediatric MB subgroups may provide a powerful tool for individualized therapies and identification of children with increased risk of complications.
Prediction of Cortical Bone Thickness Variations in the Tibial Diaphysis of Running Rats
Authors: George Daniel , Pallu Stéphane , Bourzac Céline , Wazzani Rkia , Allena Rachele , Rémond Yves , Portier Hugues
Published: February 2022

A cell-mechanobiological model is used for the prediction of bone density variation in rat tibiae under medium and high mechanical loads. The proposed theoretical-numerical model has only four parameters that need to be identified experimentally. It was used on three groups of male Wistar rats under sedentary, moderate intermittent and continuous running scenarios over an eight week period. The theoretical numerical model was able to predict an increase in bone density under intermittent running (medium intensity mechanical load) and a decrease of bone density under continuous running (higher intensity mechanical load). The numerical predictions were well correlated with the experimental observations of cortical bone thickness variations, and the experimental results of cell activity enabled us to validate the numerical results predictions. The proposed model shows a good capacity to predict bone density variation through medium and high mechanical loads. The mechanobiological balance between osteoblast and osteoclast activity seems to be validated and a foreseen prediction of bone density is made available.
Antigen-Presenting Cells in Psoriasis
Authors: Antal Dóra , Alimohammadi Shahrzad , Bai Péter , Szöllősi Attila Gábor , Szántó Magdolna
Published: February 2022

Psoriasis is classically considered a chronic inflammatory skin disorder, however the identification of autoantigens in its pathogenesis established it as a T cell mediated autoimmune disease. As such professional antigen-presenting cells (APCs) are key players in the development of lesions. APCs in the skin include dendritic cells, Langerhans cells and monocytes/macrophages. In addition, epidermal keratinocytes and dermal mast cells are also endowed with antigen-presenting capacity. Skin APCs have central role in the maintenance of cutaneous immune homeostasis, as well as in initiating and sustaining inflammation under pathologic conditions. In this review we discuss the functional specialization of human skin APCs that promote T cell activation and adaptive immune response during psoriasis initiation and onset.
Maggot Extract Interrupts Bacterial Biofilm Formation and Maturation in Combination with Antibiotics by Reducing the Expression of Virulence Genes
Authors: Becerikli Mustafa , Wallner Christoph , Dadras Mehran , Wagner Johannes M. , Dittfeld Stephanie , Jettkant Birger , Gestmann Falk , Mehlhorn Heinz , Mehlhorn-Diehl Tim , Lehnhardt Marcus , Behr Björn
Published: February 2022

Biofilms are aggregates of bacteria encased in an extracellular polymer matrix that acts as a diffusion barrier protecting the microbial community. Bacterial communication occurs by small signaling molecules called quorum sensing (QS) factors, which are involved in the activation of virulence genes and formation of biofilms. Larvae of the green bottle blowfly Lucilia sericata remove necrotic tissue by mechanical action (debridement) and proteolytic digestion. We produced a freeze-dried storable powder from larval extract and investigated its therapeutic effect on biofilms. Larval extract in concentrations of 6 and 12 mg/mL in combination with 0.5% antibiotics (≙50 U/mL penicillin and 50 μg/mL streptomycin) diminished free-floating (planktonic) Pseudomonas aeruginosa maintenance, while it showed no effect on Staphylococcus aureus and was not toxic to dermal cells. We established an ex vivo human dermal wound model. Larval extract in concentrations of 24 and 75 mg/mL in the presence of antibiotics (0.5%) significantly destroyed the biofilm stability of both P. aeruginosa and S. aureus biofilms. Furthermore, SEM analyses revealed crack and gap formations on P. aeruginosa. biofilm surface and decreased expression of P. aeruginosa biofilm maturation and virulence genes (lasR, rhlR and rhlA) was observed after treatment by larval extract in combination with antibiotics.
Tilting-Pad Journal Bearings—Frequency-Dependent Dynamic Coefficients and Pivot Flexibility Effects
Authors: Wagner Laurence F. , Allaire Paul E.
Published: February 2022

Tribologists have generally accepted that the dynamic modeling of tilting-pad journal bearings (TPJB) must consider the frequency dependency of the dynamic properties. Industrial compressors, turbines, and other rotating machines are subjected to instability drivers, such as blades, impellers, and seals, leading to dominant vibratory frequencies that are generally quite different from rotational frequency. Though the literature has provided related methods and numerical results, full understanding of the physics of TPJB frequency dependency is not generally available to the design community, and theorists and experimentalists are often not in agreement. This investigation hinges on a single-pad, two degree-of-freedom model that creates a basis for understanding the various geometries and operating conditions related to frequency dependency for a full bearing. The analytical results indicate that both stiffness and damping coefficients show frequency dependency, and that the dependency is primarily associated with the pad rotational damping and the flexibility of the pivot contact region that provides support for the pad. Understanding the role of pivot flexibility in combination with the fluid film provides a key to improving agreement between theory and experiment. This article is a revised and expanded version of the paper presented at the ASME 2019 Turbo Expo in Phoenix, Arizona from 17 to 21 June. The paper number was GT2019-90195 and it was titled “On the Frequency Dependency of Tilting-Pad Journal Bearings”.
Damage Evolution of Steel Fibre-Reinforced High-Performance Concrete in Low-Cycle Flexural Fatigue: Numerical Modeling and Experimental Validation
Authors: Gebuhr Gregor , Pise Mangesh , Anders Steffen , Brands Dominik , Schröder Jörg
Published: February 2022

This contribution aims to analyze the deterioration behaviour of steel fibre-reinforced high-performance concrete (HPC) in both experiments as well as numerical simulations. For this purpose, flexural tensile tests are carried out on beams with different fibre contents and suitable damage indicators are established to describe and calibrate the damage behaviour numerically using a phase-field model approach. In addition to conventional measurement methods, the tests are equipped with acoustic emission sensors in order to obtain a more precise picture of crack evolution by observing acoustic events. It is shown that, in addition to classical damage indicators, such as stiffness degradation and absorbed energy, various acoustic indicators, such as the acoustic energy of individual crack events, can also provide information about the damage progress. For the efficient numerical analysis of the overall material behaviour of fibre-reinforced HPC, a phenomenological material model is developed. The data obtained in the experiments are used to calibrate and validate the numerical model for the simulation of three-point bending beam tests. To verify the efficiency of the presented numerical model, the numerical results are compared with the experimental data, e.g., load-CMOD curves and the degradation of residual stiffness.
Analysis of Behaviors of the Railway Subgrade with a New Waterproof Seal Layer
Authors: Wang Wubin , Deng Zhixing , Niu Yunbin , Li Yandong , Huang Zhichao , Dong Minqi , Su Qian
Published: February 2022

This study proposes a new waterproof sealing layer to reduce the impact of water on subgrade beds. The proposed waterproof sealing layer is composed of a polyurethane adhesive (PA) mixture, which aims to control interlaminar deformation and prevent seepage. A variety of laboratory tests were first performed to analyze the attenuation characteristics and mechanical properties of various polyurethane polymer (PP)-improved gravel mixtures under thermohydraulic coupling effects. In addition, a waterproof performance model test of the PP-improved gravel layer was conducted to investigate its waterproof and drainage performance and hydraulic damage mechanism. Finally, the feasibility and effectiveness of the surface structure of the waterproof drainage subgrade bed containing the PA mixture was tested in combination with the treatment project of the Ciyaowan station of the Baoshen heavy-haul railway. According to the experimental and model results, (1) the waterproof layer containing the polyurethane mixture exhibited satisfactory stiffness, elasticity and flexibility. The waterproof layer containing the polyurethane mixture also controlled the deformation between layers, and its mechanical properties remained stable. (2) The waterproof layer with the dense polyurethane mixture performed well in terms of the waterproof aspect, and no infiltration occurred under cyclic load (3). Long-term field monitoring revealed that the effect of the implementation of a PP-improved gravel layer to treat mud pumping was remarkable. The settlement of the PP-improved gravel layer only reached 13.21 mm, and the settlement remained stable in the later stage.
Biotreatments Using Microbial Mixed Cultures with Crude Glycerol and Waste Pinewood as Carbon Sources: Influence of Application on the Durability of Recycled Concrete
Authors: Serrano-González Lorena , Merino-Maldonado Daniel , Antolín-Rodríguez Andrea , Lemos Paulo C. , Pereira Alice S. , Faria Paulina , Juan-Valdés Andrés , García-González Julia , Morán-del Pozo Julia Mª
Published: February 2022

Two eco-friendly healing bioproducts generated from microbial mixed cultures (MMC) for the production of polyhydroxyalkanoates (PHA) were used as surface treatments, with two residual materials used as the substrates, namely crude glycerol and pinewood bio-oil. Their ability to improve the durability of concrete samples containing recycled aggregates was assessed. To determine this protective capacity, 180 samples were analyzed using different tests, such as water penetration under pressure, capillary absorption, freeze–thaw and water droplet absorption test. Three types of conditions were used: outdoor–indoor exposure, re-application of biopolymers and application in vertical exposure conditions. The results showed reductions of up to 50% in the water penetration test and a delay in the water droplet absorption test of up to 150 times relative to the reference. The surface application of these bioproducts significantly reduced the degree of water penetration in recycled concrete, increasing its useful lifespan and proving to be a promising treatment for protecting concrete surfaces.
Influence of Build Orientation, Chamber Temperature and Infill Pattern on Mechanical Properties of 316L Parts Manufactured by Bound Metal Deposition
Authors: Gabilondo Maitane , Cearsolo Xabier , Arrue Mario , Castro Francisco
Published: February 2022

Bound Metal Deposition (BMD) is an alternative to the most common additive manufacturing (AM) technology for metal parts, Powder Bed Fusion (PBF), since the equipment used is more affordable and there are no risks due to exposure to loose powder and lasers or beams. However, the mechanical properties of parts manufactured by BMD are generally lower than those of PBF, making it necessary to study the process parameters to improve their performance. The aim of this work was to analyse the effect of different process parameters on the mechanical properties of 316L parts manufactured by BMD based on a set of specially designed experiments. The methodology followed in this research was thus based on the manufacturing of a series of samples with variations of the build orientation, infill pattern and chamber temperature followed by subsequent characterization and analysis. The microstructural analysis showed that voids were formed as a consequence of the air gaps generated between rasters during printing. It was observed that the characteristics of these macropores had a significant effect on the mechanical properties. The location, distribution and shape of these macropores depended on the alignment of rasters in each of the conditions, which varied with build orientation and infill pattern. Regarding the build orientation, horizontal parts exhibited lower porosity and considerably higher ultimate tensile strengths (UTS), approximately 160 MPa higher, than vertical samples. With respect to the infill pattern, horizontal parts with a concentric infill pattern showed triangular voids and a total porosity higher than 5%. However, samples with line infill patterns presented elongated macropores and a total porosity lower than 5%, properties that resulted in an improvement in UTS of 20 MPa, approximately. Overall, the results presented here offer a better comprehension of the effect of the BMD process parameters on mechanical properties and serve as a guideline for future work.
Guayule Natural Rubber Latex and Bi2O3 Films for X-ray Attenuating Medical Gloves
Authors: Ramirez Cadavid David A. , Layman Rick R. , Nishino Thomas , Slutzky J. Lauren , Li Zhenyu , Cornish Katrina
Published: February 2022

Existing natural latex radiation-attenuating gloves (RAGs) contain a high loading of radiation attenuation filler that reduces their mechanical properties to below Food and Drug Administration (FDA) medical glove requirements. RAGs are commonly formulated using Hevea natural rubber latex and lead-based fillers. The former can cause life-threatening allergic responses and the latter are known for their toxicity. In this work, a new lead-free RAG formulation based on circumallergenic guayule natural rubber latex (GNRL) and non-toxic radiation attenuation filler bismuth trioxide (Bi2O3) was developed. GNRL films with Bi2O3 loadings ranging from 0 to 300 PHR at different thicknesses were prepared. Radiation attenuation efficiencies (AE) at 60, 80, 100, and 120 kVp were determined and attenuation isocontour curves predicted film thickness and Bi2O3 loading required to meet or exceed the radiation attenuation requirements of ASTM D7866 and commercial RAGs. Optimal curing conditions for GNRL/Bi2O3 films with 150 PHR Bi2O3 were investigated by varying curing temperatures and time from 87 °C to 96 °C and 65 min to 90 min, respectively. In general, as the loading of the filler increased, the density of the films increased while the thickness decreased. GNRL/Bi2O3 films with 150 PHR Bi2O3 and 0.27 mm provided 5% more AE than RAG market average attenuation at the same thickness. The films with 150 PHR Bi2O3 cured under near-optimal conditions (90 °C/85 min, and 87 °C/65 min) met both the radiation attenuation standard (ASTM D7866) and the natural latex surgeon and examination glove standards (ASTM D3577 and D3578, respectively). Thus, gloves made using our formulations and protocols demonstrated potential to meet and surpass medical natural latex glove standards, offer a single product for both infection control and radiation protection instead of double-gloving, provide a greater degree of comfort to the user, and simultaneously reduce contact reactions and eliminate potential latex allergic reaction.
Flexible Manipulation of the Reflected Wavefront Using Acoustic Metasurface with Split Hollow Cuboid
Authors: Hao Limei , Chen Xi , Yan Xiaole , Li Yujia , Zhang Li , Xie You , Pang Shaofang , Chen Zhi
Published: February 2022

This work proposes a method for actively constructing acoustic metasurface (AMS) based on the split hollow cuboid (SHC) structure of local resonance, with the designed AMS flexibly manipulating the direction of reflected acoustic waves at a given frequency range. The AMS was obtained by precisely adjusting any one or two types of structural parameters of the SHC unit, which included the diameter of the split hole, the length, width, height, and shell thickness of the SHC. The simulation results showed that the AMS can flexibly manipulate the direction of the reflected acoustic waves, and the anomalous reflection angle obeys the generalized Snell’s law. Furthermore, among the five structural parameters, the AMS’s response frequency band is widest with the hole diameter and height, followed by the length and width, and narrowest with the shell thickness. It is worth noting that comprehensive manipulation of two parameters not only broadens the response frequency band, but also strengthens the effect of the anomalous reflection at the same response frequency. The subwavelength size of the AMS constructed with such a comprehensive method has the advantages of a small size, wide response band, simple preparation, and flexible modulation, and can be widely used in various fields, such as medical imaging and underwater stealth.
Microstructure Evolution and Toughening Mechanism of a Nb-18Si-5HfC Eutectic Alloy Created by Selective Laser Melting
Authors: Yao Longhui , Wang Liang , Song Xiaojiao , Cui Ran , Li Binqiang , Lv Qi , Luo Liangshun , Su Yanqing , Guo Jingjie , Fu Hengzhi
Published: February 2022

Because of their superior mechanical performance at ultra-high temperatures, refractory niobium–silicon-based alloys are attractive high-temperature structural alloys, particularly as structural components in gas turbine engines. However, the development of niobium–silicon-based alloys for applications is limited because of the trade-off between room temperature fracture toughness and high-temperature strength. Here, we report on the fabrication of a Nb-18Si alloy with dispersion of hafnium carbide (HfC) particles through selective laser melting (SLM). XRD and SEM-BSE were used to examine the effects of scanning speed on the microstructure and the phase structure of the deposited Nb-18Si-5HfC alloy. The results show that when the scanning speed rises, the solid solubility of the solid solution improves, the interlamellar spacing of eutectics slowly decrease into nano-scale magnitude, and the corresponding hafnium carbide distribution becomes more uniform. We also discover the hafnium carbide particles dispersion in the inter-lamella structure, which contributes to its high fracture toughness property of 20.7 MPa∙m1/2 at room temperature. Hardness and fracture toughness are simultaneously improved because of the control of microstructure morphology and carbide distribution.
Quantum-Inspired Interpretable AI-Empowered Decision Support System for Detection of Early-Stage Rheumatoid Arthritis in Primary Care Using Scarce Dataset
Authors: Rahimi Samira Abbasgholizadeh , Kolahdoozi Mojtaba , Mitra Arka , Salmeron Jose L. , Navali Amir Mohammad , Sadeghpour Alireza , Mir Mohammadi Seyed Amir
Published: February 2022

Rheumatoid arthritis (RA) is a chronic inflammatory and long-term autoimmune disease that can lead to joint and bone erosion. This can lead to patients’ disability if not treated in a timely manner. Early detection of RA in settings such as primary care (as the first contact with patients) can have an important role on the timely treatment of the disease. We aim to develop a web-based Decision Support System (DSS) to provide a proper assistance for primary care providers in early detection of RA patients. Using Sparse Fuzzy Cognitive Maps, as well as quantum-learning algorithm, we developed an online web-based DSS to assist in early detection of RA patients, and subsequently classify the disease severity into six different levels. The development process was completed in collaborating with two specialists in orthopedic as well as rheumatology orthopedic surgery. We used a sample of anonymous patient data for development of our model which was collected from Shohada University Hospital, Tabriz, Iran. We compared the results of our model with other machine learning methods (e.g., linear discriminant analysis, Support Vector Machines, and K-Nearest Neighbors). In addition to outperforming other methods of machine learning in terms of accuracy when all of the clinical features are used (accuracy of 69.23%), our model identified the relation of the different features with each other and gave higher explainability comparing to the other methods. For future works, we suggest applying the proposed model in different contexts and comparing the results, as well as assessing its usefulness in clinical practice.