bluuebunny/crossref_metadata_2025 huggingface dataset:
SelectMDx and Multiparametric Magnetic Resonance Imaging of the Prostate for Men Undergoing Primary Prostate Biopsy: A Prospective Assessment in a Multi-Institutional Study
Authors: Maggi Martina , Del Giudice Francesco , Falagario Ugo G. , Cocci Andrea , Russo Giorgio Ivan , Di Mauro Marina , Sepe Giuseppe Salvatore , Galasso Fabio , Leonardi Rosario , Iacona Gabriele , Carroll Peter R. , Cooperberg Matthew R. , Porreca Angelo , Ferro Matteo , Lucarelli Giuseppe , Terracciano Daniela , Cormio Luigi , Carrieri Giuseppe , De Berardinis Ettore , Sciarra Alessandro , Busetto Gian Maria
Published: April 2021

Prostate-specific antigen (PSA) testing as the sole indication for prostate biopsy lacks specificity, resulting in overdiagnosis of indolent prostate cancer (PCa) and missing clinically significant PCa (csPCa). SelectMDx is a biomarker-based risk score to assess urinary HOXC6 and DLX1 mRNA expression combined with traditional clinical risk factors. The aim of this prospective multi-institutional study was to evaluate the diagnostic accuracy of SelectMDx and its association with multiparametric magnetic resonance (mpMRI) when predicting PCa in prostate biopsies. Overall, 310 consecutive subjects were included. All patients underwent mpMRI and SelectMDx prior to prostate biopsy. SelectMDx and mpMRI showed sensitivity and specificity of 86.5% vs. 51.9%, and 73.8% vs. 88.3%, respectively, in predicting PCa at biopsy, and 87.1% vs. 61.3%, and 63.7% vs. 83.9%, respectively, in predicting csPCa at biopsy. SelectMDx was revealed to be a good predictor of PCa, while with regards to csPCa detection, it was demonstrated to be less effective, showing results similar to mpMRI. With analysis of strategies assessed to define the best diagnostic strategy to avoid unnecessary biopsy, SelectMDx appeared to be a reliable pathway after an initial negative mpMRI. Thus, biopsy could be proposed for all cases of mpMRI PI-RADS 4–5 score, and to those with Prostate Imaging-Reporting and Data System (PI-RADS) 1–3 score followed by a positive SelectMDx.
Anti-Tumor Effects of MAPK-Dependent Tumor-Selective Oncolytic Vaccinia Virus Armed with CD/UPRT against Pancreatic Ductal Adenocarcinoma in Mice
Authors: Kurosaki Hajime , Nakatake Motomu , Sakamoto Teruhisa , Kuwano Nozomi , Yamane Masato , Ishii Kenta , Fujiwara Yoshiyuki , Nakamura Takafumi
Published: April 2021

Engineered vaccinia virus serves as an oncolytic virus for cancer virotherapy. We evaluated the oncolytic characteristics of VGF- and O1-deleted recombinant mitogen-activated protein kinase (MAPK)-dependent vaccinia virus (MDRVV). We found that compared with viruses with the deletion of either gene alone, MDRVV is more attenuated in normal cells and can replicate in cancer cells that exhibit constitutive ERK1/2 activation in the MAPK pathway. We armed MDRVV with a bifunctional fusion gene encoding cytosine deaminase and uracil phosphoribosyltransferase (CD/UPRT), which converts 5-fluorocytosine (5-FC) into chemotherapeutic agents, and evaluated its oncolytic activity alone or in combination with 5-FC in human pancreatic cancer cell lines, tumor mouse models of peritoneal dissemination and liver metastasis, and ex vivo-infected live pancreatic cancer patient-derived tissues. CD/UPRT-armed MDRVV alone could efficiently eliminate pancreatic cancers, and its antitumor effects were partially enhanced in combination with 5-FC in vitro and in vivo. Moreover, the replication of MDRVV was detected in tumor cells of patient-derived, surgically resected tissues, which showed enlarged nuclei and high expression of pERK1/2 and Ki-67, and not in stromal cells. Our findings suggest that systemic injections of CD/UPRT-armed MDRVV alone or in combination with 5-FC are promising therapeutic strategies for pancreatic ductal adenocarcinoma.
Targeting Cutaneous T-Cell Lymphoma Cells by Ingenol Mebutate (PEP005) Correlates with PKCδ Activation, ROS Induction as Well as Downregulation of XIAP and c-FLIP
Authors: Sumarni Uly , Reidel Ulrich , Eberle Jürgen
Published: April 2021

New therapeutic strategies are needed for cutaneous T-cell lymphoma (CTCL), and the plant extract ingenol mebutate (PEP005) may be considered. PEP005 has been approved for actinic keratosis, and proapoptotic activities were described in different cancer cells. Here, we aimed to investigate its efficacy in four CTCL cell lines and its mode of action. While HuT-78 and HH responded with induced apoptosis as well as with loss of cell viability and cell proliferation, MyLa and SeAx remained resistant. Interestingly, both sensitive and resistant cells showed caspase-8 activation and enhanced levels of reactive oxygen species (ROS), while final caspase-3 activation was restricted to sensitive cells. Apoptosis induction was prevented by the caspase inhibitor QVD-Oph as well as by the antioxidant vitamin E. Caspase activation by PEP005 may be explained to some extent by the downregulation of the caspase antagonistic proteins c-FLIP and XIAP in sensitive cells, whereas both proteins were strongly expressed in resistant cells. Finally, PEP005 resulted in the activation of proapoptotic PKCδ, and the PKC inhibitor bisindolylmaleimide I reduced apoptosis, caspase-3 processing and ROS production, as well as restored cell viability. In conclusion, PKCδ appeared as a central player in apoptosis regulation in CTCL cells, also suggesting its therapeutic targeting.
TGF-β: Many Paths to CD103+ CD8 T Cell Residency
Authors: Qiu Zhijuan , Chu Timothy H. , Sheridan Brian S.
Published: April 2021

CD8 tissue-resident memory T (TRM) cells primarily reside in nonlymphoid tissues without recirculating and provide front-line protective immunity against infections and cancers. CD8 TRM cells can be generally divided into CD69+ CD103− TRM cells (referred to as CD103− TRM cells) and CD69+ CD103+ TRM cells (referred to as CD103+ TRM cells). TGF-β plays a critical role in the development and maintenance of CD103+ CD8 TRM cells. In this review, we summarize the current understanding of tissue-specific activation of TGF-β mediated by integrins and how it contributes to CD103+ CD8 TRM cell development and maintenance. Furthermore, we discuss the underlying mechanisms utilized by TGF-β to regulate the development and maintenance of CD103+ CD8 TRM cells. Overall, this review highlights the importance of TGF-β in regulating this unique subset of memory CD8 T cells that may shed light on improving vaccine design to target this population.
ATF3-Expressing Large-Diameter Sensory Afferents at Acute Stage as Bio-Signatures of Persistent Pain Associated with Lumbar Radiculopathy
Authors: Lin Jiann-Her , Yu Yu-Wen , Chuang Yu-Chia , Lee Cheng-Han , Chen Chih-Cheng
Published: April 2021

The mechanism of pain chronicity is largely unknown in lumbar radiculopathy (LR). The anatomical location of nerve injury is one of the important factors associated with pain chronicity of LR. Accumulating evidence has shown constriction distal to the dorsal root ganglion (DRG) caused more severe radiculopathy than constriction proximal to the DRG; thereby, the mechanism of pain chronicity in LR could be revealed by comparing the differences in pathological changes of DRGs between nerve constriction distal and proximal to the DRG. Here, we used 2 rat models of LR with nerve constriction distal or proximal to the DRG to probe how the different nerve injury sites could differentially affect pain chronicity and the pathological changes of DRG neuron subpopulations. As expected, rats with nerve constriction distal to the DRG showed more persistent pain behaviors than those with nerve constriction proximal to the DRG in 50% paw withdraw threshold, weight-bearing test, and acetone test. One day after the operation, distal and proximal nerve constriction showed differential pathological changes of DRG. The ratios of activating transcription factor3 (ATF3)-positive DRG neurons were significantly higher in rats with nerve constriction distal to DRG than those with nerve constriction proximal to DRG. In subpopulation analysis, the ratios of ATF3-immunoreactivity (IR) in neurofilament heavy chain (NFH)-positive DRG neurons significantly increased in distal nerve constriction compared to proximal nerve constriction; although, both distal and proximal nerve constriction presented increased ratios of ATF3-IR in calcitonin gene-related peptide (CGRP)-positive DRG neurons. Moreover, the nerve constriction proximal to DRG caused more hypoxia than did that distal to DRG. Together, ATF3 expression in NHF-positive DRG neurons at the acute stage is a potential bio-signature of persistent pain in rat models of LR.
Neuronal and Astrocytic Extracellular Vesicle Biomarkers in Blood Reflect Brain Pathology in Mouse Models of Alzheimer’s Disease
Authors: Delgado-Peraza Francheska , Nogueras-Ortiz Carlos J. , Volpert Olga , Liu Dong , Goetzl Edward J. , Mattson Mark P. , Greig Nigel H. , Eitan Erez , Kapogiannis Dimitrios
Published: April 2021

Circulating neuronal extracellular vesicles (NEVs) of Alzheimer’s disease (AD) patients show high Tau and β-amyloid (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. To validate EV proteins as AD biomarkers, we immunocaptured NEVs and AEVs from plasma collected from fifteen wild type (WT), four 2xTg-AD, nine 5xFAD, and fifteen 3xTg-AD mice and assessed biomarker relationships with brain tissue levels. NEVs from 3xTg-AD mice had higher total Tau (p = 0.03) and p181-Tau (p = 0.0004) compared to WT mice. There were moderately strong correlations between biomarkers in NEVs and cerebral cortex and hippocampus (total Tau: cortex, r = 0.4, p = 0.009; p181-Tau: cortex, r = 0.7, p < 0.0001; hippocampus, r = 0.6, p < 0.0001). NEVs from 5xFAD compared to other mice had higher Aβ42 (p < 0.005). NEV Aβ42 had moderately strong correlations with Aβ42 in cortex (r = 0.6, p = 0.001) and hippocampus (r = 0.7, p < 0.0001). AEV C1q was elevated in 3xTg-AD compared to WT mice (p = 0.005); AEV C1q had moderate-strong correlations with C1q in cortex (r = 0.9, p < 0.0001) and hippocampus (r = 0.7, p < 0.0001). Biomarkers in circulating NEVs and AEVs reflect their brain levels across multiple AD mouse models supporting their potential use as a “liquid biopsy” for neurological disorders.
Chemical Inhibitors of Dynamin Exert Differential Effects in VEGF Signaling
Authors: Basagiannis Dimitris , Zografou Sofia , Goula Evangeli , Gkeka Despoina , Kolettas Evangelos , Christoforidis Savvas
Published: April 2021

VEGFR2 is the main receptor and mediator of the vasculogenic and angiogenic activity of VEGF. Activated VEGFR2 internalizes through clathrin-mediated endocytosis and macropinocytosis. As dynamin is a key regulator of the clathrin pathway, chemical inhibitors of dynamin are commonly used to assess the role of the clathrin route in receptor signaling. However, drugs may also exert off-target effects. Here, we compare the effects of three dynamin inhibitors, dynasore, dyngo 4a and dynole, on VEGFR2 internalization and signaling. Although these drugs consistently inhibit clathrin-mediated endocytosis of both transferrin (a typical cargo of this route) and VEGFR2, surprisingly, they exert contradictory effects in receptor signaling. Thus, while dynasore has no effect on phosphorylation of VEGFR2, the other two drugs are strong inhibitors. Furthermore, although dyngo does not interfere with phosphorylation of Akt, dynasore and dynole have a strong inhibitory effect. These inconsistent effects suggest that the above dynamin blockers, besides inhibiting dynamin-dependent endocytosis of VEGFR2, exert additional inhibitory effects on signaling that are independent of endocytosis; i.e., they are due to off-target effects. Using a recently developed protocol, we comparatively validate the specificity of two endocytic inhibitors, dynasore and EIPA. Our findings highlight the importance of assessing whether the effect of an endocytic drug on signaling is specifically due to its interference with endocytosis or due to off-targets.
Abdominal Obesity-Related Disturbance of Insulin Sensitivity Is Associated with CD8+ EMRA Cells in the Elderly
Authors: Boßlau Tim K. , Wasserfurth Paulina , Krüger Britta , Reichel Thomas , Palmowski Jana , Nebl Josefine , Weyh Christopher , Schenk Alexander , Joisten Niklas , Stahl Frank , Thoms Stefanie , Gebhardt Kristina , Hahn Andreas , Krüger Karsten
Published: April 2021

Aging and overweight increase the risk of developing type 2 diabetes mellitus. In this cross-sectional study, we aimed to investigate the potential mediating role of T-EMRA cells and inflammatory markers in the development of a decreased insulin sensitivity. A total of 134 healthy older volunteers were recruited (age 59.2 (SD 5.6) years). T cell subpopulations were analyzed by flow cytometry. Furthermore, body composition, HOMA-IR, plasma tryptophan (Trp) metabolites, as well as cytokines and adipokines were determined. Using subgroup and covariance analyses, the influence of BMI on the parameters was evaluated. Moreover, correlation, multiple regression, and mediation analyses were performed. In the subgroup of participants with obesity, an increased proportion of CD8+EMRA cells and elevated concentrations of plasma kynurenine (KYN) were found compared to the lower-weight subgroups. Linear regression analysis revealed that an elevated HOMA-IR could be predicted by a higher proportion of CD8+EMRA cells and KYN levels. A mediation analysis showed a robust indirect effect of the Waist-to-hip ratio on HOMA-IR mediated by CD8+EMRA cells. Thus, the deleterious effects of abdominal obesity on glucose metabolism might be mediated by CD8+EMRA cells in the elderly. Longitudinal studies should validate this assumption and analyze the suitability of CD8+EMRA cells as early predictors of incipient prediabetes.
Future Challenges in Research in Children with Neurodevelopmental Disorders
Authors: Romero-Ayuso Dulce
Published: April 2021

The prevalence of neurodevelopmental disorders exceeds 15% worldwide, and often they are associated with other neurological disorders [...]
Dynamic Reversible Evolution of Wrinkles on Floating Polymer Films under Magnetic Control
Authors: Jiang Chenchen , Han Xue , Wang Juanjuan , Li Lele , Liu Enping , Lu Conghua
Published: April 2021

In this paper, we present a simple and versatile method to dynamically and reversibly tailor surface wrinkles on a floating polymer film by combining a magnetic droplet and neodymium magnet. The magnetic force from the attraction of the neodymium magnet to the magnetic droplet is the main reason for surface instabilities of floating polymer films, which can induce radial stress in the radial direction, and further, compressive stress in the circumferential direction. This compressive stress can trigger not only floating film wrinkling but also a wrinkle-fold transition. Surface morphologies on the floating polymer film have been systematically studied, by varying the distance between the magnetic droplet and neodymium magnet, polymer film thickness, and magnetic droplet volume. With the decrease in the distance between a magnetic droplet and a neodymium magnet, the decrease in polymer film thickness, and the increase in the magnetic droplet volume, the wrinkle numbers increase and even a wrinkle-fold transition happens. Additionally, the coupling effect of multiple magnetic droplets on the floating film has also been used to achieve novel surface wrinkle patterns, which greatly widens the applications of surface wrinkling.
Microstructure and Shear Strength of Brazing High Entropy TiZrHfNbMo Alloy and Si3N4 Ceramics Joints
Authors: Wang Xiaohong , Dong Duo , Yang Xiaohong , Huang Peng , Shi Kangqiao , Ma Tengfei , Zhu Dongdong , Liu Li
Published: April 2021

The effects of different brazing processes on the interfacial microstructure and shear strength of TiZrHfNbMo high-entropy alloy (HEAS) and Si3N4 ceramic brazed joints were studied. There is no obvious defect in a brazed TiZrHfNbMo HEAS/AgCuTi/Si3N4 ceramic joint, and the two materials have good metallurgical bonding. The typical interface microstructure is Si3N4/Ti5Si3/Ag solid solution +Cu (s,s)+ CuTi/Cu2Ti/Cu4Ti + TiCu(Hf,Zr)NbMo/TiZrHfNbMo HEAs. With the increase of brazing temperature, the dispersed CuTi phase agglomerates in the brazed joint, and acts as the nucleate of the Cu-based solid solution. The thickness of the reaction layer increases with the increase of phases in the reaction layer on both sides of the joint. When the brazing temperature is 800 °C, 820 °C, 840 °C and 860 °C, the shear strength of the brazed joint is 30 MPa, 72 MPa, 86 MPa and 21 MPa, respectively. The formation of CuTi and Ti5Si3 intermetallic compounds increases the thickness of the reaction layer, and improves the strength of the joint. However, excessive CuTi and Ti5Si3 intermetallic compounds lead to a significant decrease in joint strength. The grain coarsening of the joint can also affect the strength of the joint.
Erratum: Jiang et al. Localization Accuracy of Ultrasound-Actuated Needle with Color Doppler Imaging. Diagnostics 2020, 10, 1020
Authors: Jiang Tingyi , McLeod Graeme , Huang Zhihong , Zhu Xinle , Jiao Yang , Li Xinze , Shen Zhitian , Cui Yaoyao
Published: April 2021

The authors wish to correct the following erratum in this paper [...]
A Multi-Tiered Framework for Insider Threat Prevention
Authors: Alsowail Rakan A. , Al-Shehari Taher
Published: April 2021

As technologies are rapidly evolving and becoming a crucial part of our lives, security and privacy issues have been increasing significantly. Public and private organizations have highly confidential data, such as bank accounts, military and business secrets, etc. Currently, the competition between organizations is significantly higher than before, which triggers sensitive organizations to spend an excessive volume of their budget to keep their assets secured from potential threats. Insider threats are more dangerous than external ones, as insiders have a legitimate access to their organization’s assets. Thus, previous approaches focused on some individual factors to address insider threat problems (e.g., technical profiling), but a broader integrative perspective is needed. In this paper, we propose a unified framework that incorporates various factors of the insider threat context (technical, psychological, behavioral and cognitive). The framework is based on a multi-tiered approach that encompasses pre, in and post-countermeasures to address insider threats in an all-encompassing perspective. It considers multiple factors that surround the lifespan of insiders’ employment, from the pre-joining of insiders to an organization until after they leave. The framework is utilized on real-world insider threat cases. It is also compared with previous work to highlight how our framework extends and complements the existing frameworks. The real value of our framework is that it brings together the various aspects of insider threat problems based on real-world cases and relevant literature. This can therefore act as a platform for general understanding of insider threat problems, and pave the way to model a holistic insider threat prevention system.
Risk Assessment for the Use of COTS Devices in Space Systems under Consideration of Radiation Effects
Authors: Budroweit Jan , Patscheider Hagen
Published: April 2021

In this paper, a new approach is presented to assess the risk of using commercial off-the-shelf (COTS) devices in space systems under consideration of radiation effects that can dramatically affect reliability and performance. In the NewSpace era, the use of COTS has become mandatory, since typical space-qualified (class-1) electrical, electronic and electromechanical (EEE) components for space missions are no longer attractive due to their extremely high costs, long lead times and low performance. This paper sets out the usual constraints for COTS devices and proposes a guideline on how to select non-space-qualified components and when class-1 EEE devices are recommended for use.
Design and Verification of a Charge Pump in Local Oscillator for 5G Applications
Authors: Guo Rui , Lu Zhenghao , Hu Shaogang , Yu Qi , Rong Limei , Liu Yang
Published: April 2021

A charge pump (CP) that has low current mismatch to reduce the locking time of the Phase-Locked Loop (PLL) is proposed. The design is promising in 5G applications with the capabilities of fast settling and low power consumption. In this design, a charge pump architecture consists of an operational power amplifier (OPA), switches, three D flip-flops (DFFs) and passive devices. A phase error compensation technique is introduced in the charge pump to reduce the locking time. The current mismatch, which is mainly due to the leakage current, is below 1% for a large output voltage headroom of 84% of the supply voltage. An 18.4% reduction in the settling time is realized by the proposed design.
Inferring the Phylogeny and Divergence of Chinese Curcuma (Zingiberaceae) in the Hengduan Mountains of the Qinghai–Tibet Plateau by Reduced Representation Sequencing
Authors: Liang Heng , Deng Jiabin , Gao Gang , Ding Chunbang , Zhang Li , Xu Ke , Wang Hong , Yang Ruiwu
Published: April 2021

Clarifying the genetic relationship and divergence among Curcuma L. (Zingiberaceae) species around the world is intractable, especially among the species located in China. In this study, Reduced Representation Sequencing (RRS), as one of the next generation sequences, has been applied to infer large scale genotyping of major Chinese Curcuma species which present little differentiation of morphological characteristics and genetic traits. The 1295 high-quality SNPs (reduced-filtered SNPs) were chosen from 997,988 SNPs of which were detected from the cleaned 437,061 loci by RRS to investigate the phylogeny and divergence among eight major Curcuma species locate in the Hengduan Mountains of the Qinghai–Tibet Plateau (QTP) in China. The results showed that all the population individuals were clustered together within species, and species were obviously separated; the clustering results were recovered in PCA (Principal Component Analysis); the phylogeny was (((((C. Phaeocaulis, C. yunnanensis), C. kwangsiensis), (C. amarissima, C. sichuanensis)), C. longa), (C. wenyujin, C. aromatica)); Curcuma in China originated around ~7.45 Mya (Million years ago) in the Miocene, and interspecific divergence appeared at ca. 4–2 Mya, which might be sped up rapidly along with the third intense uplift of QTP.
An Analytical Solution for Unsteady Laminar Flow in Tubes with a Tapered Wall Thickness
Authors: Wiens Travis , Etminan Elnaz
Published: April 2021

Transient fluid flows through tubes are critical in such topics as water hammer, ram pumps and pipeline dynamics. While analytical solutions exist in the literature for simple geometries such as tapered and non-tapered tube diameters, one area that is lacking is the case where the wave speed changes along the length. An example of this is a flexible pipe with a tapered wall thickness. In order to calculate the transient pressure response of such a system, this previously required a computationally expensive gridded method of characteristics (MOC) solution. This paper describes an analytical solution to the dynamic laminar flow of liquid in a tube where the wave speed varies along its length. This frequency-domain solution includes frequency-dependent friction effects. A comparison to a method of characteristics (MOC) solution is used to verify the solution. The paper also discusses some numerical issues and provides an approximate method that can be used for high-frequency calculations where limited numerical precision can cause errors. Finally, a preliminary comparison of the computational performance is presented, in which the new method is an order of magnitude faster to calculate than an MOC solution.
The Role of Knockout Olfactory Receptor Genes in Odor Discrimination
Authors: Concas Maria Pina , Cocca Massimiliano , Francescatto Margherita , Battistuzzi Thomas , Spedicati Beatrice , Feresin Agnese , Morgan Anna , Gasparini Paolo , Girotto Giorgia
Published: April 2021

To date, little is known about the role of olfactory receptor (OR) genes on smell performance. Thanks to the availability of whole-genome sequencing data of 802 samples, we identified 41 knockout (KO) OR genes (i.e., carriers of Loss of Function variants) and evaluated their effect on odor discrimination in 218 Italian individuals through recursive partitioning analysis. Furthermore, we checked the expression of these genes in human and mouse tissues using publicly available data and the presence of organ-related diseases in human KO (HKO) individuals for OR expressed in non-olfactory tissues (Fisher test). The recursive partitioning analysis showed that age and the high number (burden) of OR-KO genes impact the worsening of odor discrimination (p-value < 0.05). Human expression data showed that 33/41 OR genes are expressed in the olfactory system (OS) and 27 in other tissues. Sixty putative mouse homologs of the 41 humans ORs have been identified, 58 of which are expressed in the OS and 37 in other tissues. No association between OR-KO individuals and pathologies has been detected. In conclusion, our work highlights the role of the burden of OR-KO genes in worse odor discrimination.
Seismic Vulnerability Assessment in Ranau, Sabah, Using Two Different Models
Authors: binti Abd Razak Janatul Aziera , bin Rambat Shuib , binti Che Ros Faizah , Shi Zhongchao , bin Mazlan Saiful Amri
Published: April 2021

Sabah is prone to seismic activities due to its location, being geographically located near the boundaries of three major active tectonic plates; the Eurasian, India-Australia, and Philippine-Pacific plates. The 6.0 Mw earthquake that occurred in Ranau, Sabah, on 15 June 2015 which caused 18 casualties, all of them climbers of Mount Kinabalu, raised many issues, primarily the requirements for seismic vulnerability assessment for this region. This study employed frequency ratio (FR)–index of entropy (IoE) and a combination of (FR-IoE) with an analytical hierarchy process (AHP) to map seismic vulnerability for Ranau, Sabah. The results showed that the success rate and prediction rate for the areas under the relative operating characteristic (ROC) curves were 0.853; 0.856 for the FR-IoE model and 0.863; 0.906 for (FR-IoE) AHP, respectively, with the highest performance achieved using the (FR-IoE) AHP model. The vulnerability maps produced were classified into five classes; very low, low, moderate, high, and very high seismic vulnerability. Seismic activities density ratio analysis performed on the final seismic vulnerability maps showed that high seismic activity density ratios were observed for high vulnerability zones with the values of 9.119 and 8.687 for FR-IoE and (FR-IoE) AHP models, respectively.
Inferring Urban Land Use from Multi-Source Urban Mobility Data Using Latent Multi-View Subspace Clustering
Authors: Liu Qiliang , Huan Weihua , Deng Min , Zheng Xiaolin , Yuan Haotao
Published: April 2021

In the era of big data, vast urban mobility data introduce new opportunities to infer urban land use from the perspective of social function. Most existing works only derive land use information from a single type of urban mobility dataset, which is typically biased and results in difficulty obtaining a comprehensive view of urban land use. It remains challenging to fuse high-dimensional and noisy multi-source urban mobility data to infer urban land use. This study aimed to infer urban land use from multi-source urban mobility data using latent multi-view subspace clustering. The variation in the number of origin/destination points over time was initially used to characterize land use types. Then, a latent multi-view representation was applied to construct the common underlying structure shared by multi-source urban mobility data and effectively deal with noise. Finally, based on the latent multi-view representation, the subspace clustering method was used to infer the land use types. Experiments on taxi trajectory data and bus smart card data in Beijing reveal that, compared with the method using a single type of urban mobility dataset and the weighted fusion method, the approach presented in this study obtains the highest detection rate of land use. The urban land use inferred in this study provides calibration and reference for urban planning.
Collective and Informal Learning in the ViewpointS Interactive Medium
Authors: Lemoisson Philippe , Cerri Stefano A. , Douzal Vincent , Dugénie Pascal , Tonneau Jean-Philippe
Published: April 2021

Collective learning has been advocated to be at the source for innovation, particularly as serendipity seems historically to have been the driving force not only behind innovation, but also behind scientific discovery and artistic creation. Informal learning is well known to represent the most significant learning effects in humans, far better than its complement: formal learning with predefined objectives. We have designed an approach—ViewpointS—based on a digital medium—the ViewpointS Web Application—that enables and enhances the processes for sharing knowledge within a group and is equipped with metrics aimed at assessing collective and informal learning. In this article, we introduce by giving a brief state of the art about collective and informal learning, then outline our approach and medium, and finally, present and exploit a real-life experiment aimed at evaluating the ViewpointS approach and metrics.
Renal Replacement Therapy in Patients with Influenza Pneumonia Related Acute Respiratory Distress Syndrome
Authors: Chang Ko-Wei , Leu Shaw-Woei , Lin Shih-Wei , Liang Shinn-Jye , Yang Kuang-Yao , Chan Ming-Cheng , Chen Wei-Chih , Hu Han-Chung , Fang Wen-Feng , Chen Yu-Mu , Sheu Chau-Chyun , Tsai Ming-Ju , Wang Hao-Chien , Chien Ying-Chun , Peng Chung-Kan , Wu Chieh-Liang , Kao Kuo-Chin ,   TSIRC (Taiwan Severe Influenza Research Consortium)
Published: April 2021

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) increases the mortality of acute respiratory distress syndrome (ARDS) patients. The aim of this study was to investigate the outcomes and predictors of RRT in patients with influenza pneumonia-related ARDS. This retrospective cohort study includes patients from eight tertiary referral centers in Taiwan between January and March 2016, and all 282 patients with influenza pneumonia-related ARDS were enrolled. Thirty-four patients suffered from AKI requiring RRT, while 16 patients had underlying end stage renal disease (ESRD). The 30- and 60-day mortality rates were significantly higher in patients with AKI requiring RRT compared with those not requiring RRT (50.0% vs. 19.8%, p value < 0.001; 58.8% vs. 27.2%, p value = 0.001, respectively), but the patients with ESRD had no significant difference in mortality (12.5% vs. 19.8%, p value = 0.744; 31.3% vs. 27.2%, p value = 0.773, respectively). The predictors for AKI requiring RRT included underlying chronic liver disease and C-reactive protein. The mortality predictors for patients with AKI requiring RRT included the pneumonia severity index, tidal volume, and continuous renal replacement therapy. In this study, patients with influenza pneumonia-related ARDS with AKI requiring RRT had significantly higher mortality compared with other patients.
POLG Gene Variants in Cervical Cancer Patients and Their Associations with Clinical and Pathomorphological Tumor Characteristics
Authors: Golubickaite Ieva , Ugenskiene Rasa , Ziliene Egle , Beniusyte Jurgita , Inciura Arturas , Poskiene Lina , Juozaityte Elona
Published: April 2021

Cervical cancer is one of the most common cancers in women worldwide. Human papillomaviruses are known to be the main, but not the only risk factor, of this cancer type. Despite all the knowledge on this cancer type, it is still a challenge to predict the course of the disease, and therefore, minimally invasive biomarkers are needed. This study aimed to analyze single-nucleotide variants in the POLG gene and assess the associations with tumor phenotype and patient outcome. A total of 172 cervical cancer patients were included in this study. Clinical and tumor data were gathered from medical records retrospectively. Single nucleotide variations were determined using TaqMan probes with Real-Time PCR. Significant associations between POLG rs3087374 and cervical cancer patients’ tumor histological type, stage, and tumor size were determined. The CA genotype and A allele of rs3087374 increased the probability of adenocarcinoma histological tumor type, IIIA stage, and T3 tumor size compared to CC genotype and C allele, respectively. Furthermore, patients with AA genotype in rs2072267 had longer metastasis-free survival than those with the GG genotype. Our data suggest that mitochondrial polymerase gamma encoded by nuclear POLG gene is important for specific tumor phenotype formation and patient outcome in cervical cancer.
Serum Calcium Level as a Useful Surrogate for Risk of Elevated Intraocular Pressure
Authors: Chang Yu-Min , Chen Jiann-Torng , Tai Ming-Cheng , Chen Wei-Liang , Chen Ying-Jen
Published: April 2021

Background: Uncontrolled intraocular pressure (IOP) plays a principal role in the deterioration of glaucoma, and the intraocular pressure is also accepted as the most important modifiable factor. Calcium ion has been found to play a vital role in regulating the resistance of the trabecular meshwork in humans. However, the relationship between serum total calcium and IOP has not been well-established. Methods: We investigated the association between serum total calcium and the IOP in a large population (14,037 eligible participants, consisting of 7712 men and 6325 women, were included) at the Tri-Service General Hospital from 2010 to 2016. Several models of covariate adjustments associated with IOP were designed. Univariate and multivariate regression analysis was performed for gender differences in the association between the serum total calcium level and IOP. Results: There was a significant relationship between serum total calcium levels and IOP in women and men with a β coefficient of 0.050 (95% confidence interval (CI), 0.030–0.069) and 0.025 (95%CI, 0.007–0.043). Notably, participants in the highest tertiles of serum total calcium levels had significantly higher IOP, in both the male and female participants. Conclusions: Our study shows that IOP is significantly associated with serum total calcium levels in a large Asian population. This study supports the notion that serum total calcium may play an important role in groups at high risk for elevated IOP.
Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients
Authors: Kim Sehwa , Lee Yoonseok , Bang Soo Min , Bak Haein , Yim Sun Young , Lee Young Sun , Yoo Yang Jae , Jung Young Kul , Kim Ji Hoon , Seo Yeon Seok , Yim Hyung Joon , Um Soon Ho , Byun Kwan Soo , Yeon Jong Eun
Published: April 2021

Potent antiviral agents effectively reduce liver-related events in patients with chronic hepatitis B. This study aimed to determine whether alanine aminotransferase normalization using potent antiviral agents was related to hepatocellular carcinoma development. From 2007 to 2017, we included 610 patients with chronic hepatitis B who received entecavir or tenofovir disoproxil fumarate. The patients were divided into the alanine aminotransferase normalization group (Gr.1) and non-normalization group (Gr.2) within a year of potent antiviral treatment. Liver-related events included hepatic encephalopathy, variceal bleeding, and ascites. The mortality rate and hepatocellular carcinoma incidence were investigated for each group. The patients who showed ALT normalization at 1 year of treatment were 397 (65.1%) of 610. During a median follow-up period of 86 months, 65 (10.7%) patients developed hepatocellular carcinoma. The cumulative incidence of hepatocellular carcinoma was significantly lower in Gr.1 than in Gr.2 (p < 0.001). Risk factors for alanine aminotransferase non-normalization were body mass index, cholesterol, and liver cirrhosis at baseline. Male sex, age, platelet level, alcohol use, presence of cirrhosis at baseline, and non-normalization after 1 year of treatment were independent risk factors for hepatocellular carcinoma. Alanine aminotransferase normalization within 1 year of initiating antiviral agents reduces the risk of hepatocellular carcinoma development.
Autoimmune Diseases and COVID-19 as Risk Factors for Poor Outcomes: Data on 13,940 Hospitalized Patients from the Spanish Nationwide SEMI-COVID-19 Registry
Authors: Ayala Gutiérrez María , Rubio-Rivas Manuel , Romero Gómez Carlos , Montero Sáez Abelardo , Pérez de Pedro Iván , Homs Narcís , Ayuso García Blanca , Cuenca Carvajal Carmen , Arnalich Fernández Francisco , Beato Pérez José , Vargas Núñez Juan , Letona Giménez Laura , Suárez Fernández Carmen , Méndez Bailón Manuel , Tuñón de Almeida Carlota , González Moraleja Julio , de Guzmán García-Monge Mayte , Helguera Amezua Cristina , Fidalgo Montero María , Giner Galvañ Vicente , Gil Sánchez Ricardo , Collado Sáenz Jorge , Boixeda Ramon , Ramos Rincón José , Gómez Huelgas Ricardo ,   on behalf of the SEMI-COVID-19 Network
Published: April 2021

(1) Objectives: To describe the clinical characteristics and clinical course of hospitalized patients with COVID-19 and autoimmune diseases (ADs) compared to the general population. (2) Methods: We used information available in the nationwide Spanish SEMI-COVID-19 Registry, which retrospectively compiles data from the first admission of adult patients with COVID-19. We selected all patients with ADs included in the registry and compared them to the remaining patients. The primary outcome was all-cause mortality during admission, readmission, and subsequent admissions, and secondary outcomes were a composite outcome including the need for intensive care unit (ICU) admission, invasive and non-invasive mechanical ventilation (MV), or death, as well as in-hospital complications. (3) Results: A total of 13,940 patients diagnosed with COVID-19 were included, of which 362 (2.6%) had an AD. Patients with ADs were older, more likely to be female, and had greater comorbidity. On the multivariate logistic regression analysis, which involved the inverse propensity score weighting method, AD as a whole was not associated with an increased risk of any of the outcome variables. Habitual treatment with corticosteroids (CSs), age, Barthel Index score, and comorbidity were associated with poor outcomes. Biological disease-modifying anti-rheumatic drugs (bDMARDs) were associated with a decrease in mortality in patients with AD. (4) Conclusions: The analysis of the SEMI-COVID-19 Registry shows that ADs do not lead to a different prognosis, measured by mortality, complications, or the composite outcome. Considered individually, it seems that some diseases entail a different prognosis than that of the general population. Immunosuppressive/immunoregulatory treatments (IST) prior to admission had variable effects.
Current State of Analgesia and Sedation in the Pediatric Intensive Care Unit
Authors: Egbuta Chinyere , Mason Keira P.
Published: April 2021

Critically ill pediatric patients often require complex medical procedures as well as invasive testing and monitoring which tend to be painful and anxiety-provoking, necessitating the provision of analgesia and sedation to reduce stress response. Achieving the optimal combination of adequate analgesia and appropriate sedation can be quite challenging in a patient population with a wide spectrum of ages, sizes, and developmental stages. The added complexities of critical illness in the pediatric population such as evolving pathophysiology, impaired organ function, as well as altered pharmacodynamics and pharmacokinetics must be considered. Undersedation leaves patients at risk of physical and psychological stress which may have significant long term consequences. Oversedation, on the other hand, leaves the patient at risk of needing prolonged respiratory, specifically mechanical ventilator, support, prolonged ICU stay and hospital admission, and higher risk of untoward effects of analgosedative agents. Both undersedation and oversedation put critically ill pediatric patients at high risk of developing PICU-acquired complications (PACs) like delirium, withdrawal syndrome, neuromuscular atrophy and weakness, post-traumatic stress disorder, and poor rehabilitation. Optimal analgesia and sedation is dependent on continuous patient assessment with appropriately validated tools that help guide the titration of analgosedative agents to effect. Bundled interventions that emphasize minimizing benzodiazepines, screening for delirium frequently, avoiding physical and chemical restraints thereby allowing for greater mobility, and promoting adequate and proper sleep will disrupt the PICU culture of immobility and reduce the incidence of PACs.
Numerical Buckling Analysis of Hybrid Honeycomb Cores for Advanced Helmholtz Resonator Liners
Authors: Neubauer Moritz , Dannemann Martin , Kucher Michael , Bleil Niklas , Wollmann Tino , Modler Niels
Published: April 2021

In order to realize novel acoustic liners, honeycomb core structures specially adapted to these applications are required. For this purpose, various design concepts were developed to create a hybrid cell core by combining flexible wall areas based on thermoplastic elastomer films and rigid honeycomb areas made of fiber-reinforced thermoplastics. Within the scope of the presented study, a numerical approach was introduced to analyze the global compressive failure of the hybrid composite core structure, considering local buckling and composite failure according to Puck and Cuntze. Therefore, different geometrical configurations of fiber-reinforced tapes were compared with respect to their deformation as well as their resulting failure behavior by means of a finite element analysis. The resulting compression strength obtained by a linear buckling analysis agrees largely with calculated strengths of the more elaborate application of the failure criteria according to Puck and Cuntze, which were implemented in the framework of a nonlinear buckling analysis. The findings of this study serve as a starting point for the realization of the manufacturing concept, for the design of experimental tests of hybrid composite honeycomb core structures, and for further numerical investigations considering manufacturing as well as material specific aspects.
Maternal Cultural Orientation and Speech Sound Production in Spanish/English Dual Language Preschoolers
Authors: Montanari Simona , Mayr Robert , Subrahmanyam Kaveri
Published: April 2021

Empirical work has shown that maternal education is related to children’s language outcomes, especially in the societal language, among Spanish-English bilingual children growing up in the U.S. However, no study thus far has assessed the links between maternal cultural orientation and children’s speech sound production. This paper explores whether mothers’ orientation to American (acculturation) and Mexican culture (enculturation) and overall linear acculturation are related to children’s accuracy of production of consonants, of different sound classes, and of phonemes shared and unshared between languages in both English and Spanish at age 4;6 (4 years and 6 months). The results reveal a link between maternal acculturation and children’s segmental accuracy in English, but no relation was found between mothers’ enculturation and children’s speech sound production in Spanish. We interpreted the results in English as suggesting that more American-oriented mothers may have been using more English with their children, boosting their English production abilities and promoting English speech sound development. At the same time, we speculate that the results in Spanish were possibly due to the high and homogeneous levels of Mexican orientation among mothers, to language input differences attributable to distinct cultural practices, or to the status of Spanish as a minority language.
The Role of Tumor-Derived Exosomes in the Abscopal Effect and Immunotherapy
Authors: Shan Zechen , Wang Hongmei , Zhang Yujuan , Min Weiping
Published: April 2021

Exosomes are microvesicles that can be secreted by various cells and carry a variety of contents; thus, they play multiple biological functions. For instance, the tumor-derived exosomes (TEXs) have been proven to have the effect of immunostimulatory in addition to immunosuppression, making TEXs attractive in clinical immunotherapy and targeted therapy for cancer patients. In addition, TEXs as biomarkers have important clinical diagnostic and prognostic value. Recently, TEXs have been recognized to play important roles in the abscopal effect (AbE), a newly discovered mechanism by which the distant tumors are effectively targeted and repressed during immunotherapy and radiotherapy. Therefore, TEXs has demonstrated great clinical potential in the diagnosis, prognosis and treatment of cancer patients in the future. This review summarizes and discusses the role of TEXs in clinical therapy and their role in AbE in recent studies.
Effects of Hemispheric Stroke Localization on the Reorganization of Arm Movements within Different Mechanical Environments
Authors: Pellegrino Laura , Coscia Martina , Pierella Camilla , Giannoni Psiche , Cherif Amel , Mugnosso Maddalena , Marinelli Lucio , Casadio Maura
Published: April 2021

This study investigated how stroke’s hemispheric localization affects motor performance, spinal maps and muscle synergies while performing planar reaching with and without assistive or resistive forces. A lesion of the right hemisphere affected performance, reducing average speed and smoothness and augmenting lateral deviation in both arms. Instead, a lesion of the left hemisphere affected the aiming error, impairing the feedforward control of the ipsilesional arm. The structure of the muscle synergies had alterations dependent on the lesion side in both arms. The applied force fields reduced the differences in performance and in muscle activations between arms and among populations. These results support the hypotheses of hemispheric specialization in movement control and identify potential significant biomarkers for the design of more effective and personalized rehabilitation protocols.
Energy Recovery of Agricultural Residues: Incorporation of Vine Pruning in the Production of Biomass Pellets with ENplus® Certification
Authors: Nunes Leonel J. R. , Loureiro Liliana M. E. F. , Sá Letícia C. R. , Matias João C. O. , Ferraz Ana I. O. F. , Rodrigues Ana C. P. B.
Published: April 2021

The use of residual biomass of forest and/or agricultural origin is an increasingly common issue regarding the incorporation of materials that, until recently, were out of the typical raw material supply chains for the production of biomass pellets, mainly due to the quality constraints that some of these materials present. The need to control the quality of biomass-derived fuels led to the development of standards, such as ENplus®, to define the permitted limits for a set of parameters, such as the ash or alkali metal content. In the present study, samples of vine pruning, and ENplus®-certified pellets were collected and characterized, and the results obtained were compared with the limits presented in the standard. The values presented from vine pruning approximated the values presented by Pinus pinaster wood, the main raw material used in the production of certified pellets in Portugal, except for the values of ash, copper (Cu), and nitrogen (N) contents, with vine pruning being out of the qualifying limits for certification. However, it was found that the incorporation of up to 10% of biomass from vine pruning allowed the fulfillment of the requirements presented in the ENplus® standard, indicating a path for the implementation of circular economy processes in the wine industry.