bluuebunny/crossref_metadata_2025 huggingface dataset:
Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers
Authors: Ciciriello Fabiana , Bijvelds Marcel J. C. , Alghisi Federico , Meijsen Kelly F. , Cristiani Luca , Sorio Claudio , Melotti Paola , Fiocchi Alessandro G. , Lucidi Vincenzina , De Jonge Hugo R.
Published: April 2022

Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows separate measurement of CFTR-dependent chloride or bicarbonate transport, was used to assess the effect of ELX/TEZ/IVA on two rare CFTR variants. Methods: Intestinal organoid cultures were established from rectal biopsies of CF patients carrying the rare missense mutations E193K or R334W paired with F508del. The effect of the CFTR modulator combination ELX/TEZ/IVA on CFTR-mediated Cl− and HCO3− secretion was assessed in organoid-derived intestinal epithelial monolayers. Non-CF organoids were used for comparison. Clinical biomarkers (sweat chloride, FEV1) were monitored in patients receiving modulator therapy. Results: ELX/TEZ/IVA markedly enhanced CFTR-mediated bicarbonate and chloride transport across intestinal epithelium of both patients. Consistent with the rescue of CFTR function in cultured intestinal cells, ELX/TEZ/IVA therapy improved biomarkers of CFTR function in the R334W/F508del patient. Conclusions: Current measurements in organoid-derived intestinal monolayers can readily be used to monitor CFTR-dependent epithelial Cl− and HCO3− transport. This technique can be explored to assess the functional consequences of rare CFTR mutations and the efficacy of CFTR modulators. We propose that this functional CFTR assay may guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations.
Deciphering of Adult Glioma Vulnerabilities through Expression Pattern Analysis of GABA, Glutamate and Calcium Neurotransmitter Genes
Authors: Nguyen Hoang Dong , Diamandis Phedias , Scott Michelle S. , Richer Maxime
Published: April 2022

Adult infiltrating gliomas are highly aggressive tumors of the central nervous system with a dismal prognosis despite intensive multimodal therapy (chemotherapy and/or radiotherapy). In this study, we studied the expression, methylation and interacting miRNA profiles of GABA-, glutamate- and calcium-related genes in 661 adult infiltrating gliomas available through the TCGA database. Neurotransmitter-based unsupervised clustering identified three established glioma molecular subgroups that parallel major World Health Organization glioma subclasses (IDH-wildtype astrocytomas, IDH-mutant astrocytomas, IDH-mutant oligodendroglioma). In addition, this analysis also defined a novel, neurotransmitter-related glioma subgroup (NT-1), mostly comprised of IDH-mutated gliomas and characterized by the overexpression of neurotransmitter-related genes. Lower expression of neurotransmission-related genes was correlated with increased aggressivity in hypomethylated IDH-wildtype tumors. There were also significant differences in the composition of the tumor inflammatory microenvironment between neurotransmission-based tumor categories, with lower estimated pools of M2-phenotype macrophages in NT-1 gliomas. This multi-omics analysis of the neurotransmission expression landscape of TCGA gliomas—which highlights the existence of neurotransmission-based glioma categories with different expression, epigenetic and inflammatory profiles—supports the existence of operational neurotransmitter signaling pathways in adult gliomas. These findings could shed new light on potential vulnerabilities to exploit in future glioma-targeting drug therapies.
Investigation of the Relationship between Cardiovascular Biomarkers and Brachial–Ankle Pulse Wave Velocity in Hemodialysis Patients
Authors: Chou Ping-Ruey , Wu Pei-Yu , Wu Ping-Hsun , Huang Teng-Hui , Huang Jiun-Chi , Chen Szu-Chia , Lee Su-Chu , Kuo Mei-Chuan , Chiu Yi-Wen , Hsu Ya-Ling , Chang Jer-Ming , Hwang Shang-Jyh
Published: April 2022

Brachial–ankle pulse wave velocity (baPWV) and cardiovascular (CV) biomarkers are correlated with clinical cardiovascular diseases (CVDs) in patients with kidney disease. However, limited studies evaluated the relationship between baPWV and CV biomarkers in hemodialysis patients. This study investigated the relationship between circulating CV biomarkers and baPWV in patients on hemodialysis. Hemodialysis patients were enrolled between August 2016 and January 2017 for the measurement of baPWV, traditional CV biomarkers, including high-sensitivity troponin-T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and novel CV biomarkers, including Galectin-3, Cathepsin D, placental growth factor, Endocan-1, and Fetuin-A. The independent association was assessed by multivariate-adjusted linear regression analysis to control for potential confounders. The final analysis included 176 patients (95 men and 81 women) with a mean age of 60 ± 11 y old. After adjusting for age and sex, hsTnT (p < 0.01), NT-proBNP (p = 0.01), Galectin-3 (p = 0.03), and Cathepsin D (p < 0.01) were significantly directly correlated with baPWV. The direct correlation with baPWV existed in multivariable linear regression models with a β of 0.1 for hsTnT and 0.1 for Cathepsin D. The direct relationship between baPWV and CV biomarkers, particularly with hsTnT and Cathepsin D, may be helpful for risk stratification of hemodialysis patients.
Intravoxel Incoherent Motion (IVIM) MR Quantification in Locally Advanced Cervical Cancer (LACC): Preliminary Study on Assessment of Tumor Aggressiveness and Response to Neoadjuvant Chemotherapy
Authors: Dolciami Miriam , Capuani Silvia , Celli Veronica , Maiuro Alessandra , Pernazza Angelina , Palaia Innocenza , Di Donato Violante , Santangelo Giusi , Rizzo Stefania Maria Rita , Ricci Paolo , Della Rocca Carlo , Catalano Carlo , Manganaro Lucia
Published: April 2022

The aim of this study was to determine whether quantitative parameters obtained from intravoxel incoherent motion (IVIM) model at baseline magnetic resonance imaging (MRI) correlate with histological parameters and response to neoadjuvant chemotherapy in patients with locally advanced cervical cancer (LACC). Methods: Twenty patients with biopsy-proven cervical cancer, staged as LACC on baseline MRI and addressed for neoadjuvant chemotherapy were enrolled. At treatment completion, tumor response was assessed with a follow-up MRI evaluated using the revised response evaluation criteria in solid tumors (RECIST; version 1.1), and patients were considered good responders (GR) if they had complete response or partial remission, and poor responders/non-responders (PR/NR) if they had stable or progressive disease. MRI protocol included conventional diffusion-weighted imaging (DWI; b = 0 and 1000 s/mm2) and IVIM acquisition using eight b-values (range: 0–1500 s/mm2). MR-images were analyzed using a dedicated software to obtain quantitative parameters: diffusion (D), pseudo-diffusion (D*), and perfusion fraction (fp) from the IVIM model; apparent diffusion coefficient (ADC) from conventional DWI. Histologic subtype, grading, and tumor-infiltrating lymphocytes (TILs) were assessed in each LACC. Results: D showed significantly higher values in GR patients (p = 0.001) and in moderate/high TILs (p = 0.018). Fp showed significantly higher values in squamous cell tumors (p = 0.006). Conclusions: D extracted from the IVIM model could represent a promising tool to identify tumor aggressiveness and predict response to therapy.
Predictors of SARS-CoV-2 IgG Spike Antibody Responses on Admission and Clinical Outcomes of COVID-19 Disease in Fully Vaccinated Inpatients: The CoVax Study
Authors: Livanou Eleni , Rouka Erasmia , Sinis Sotirios , Dimeas Ilias , Pantazopoulos Ioannis , Papagiannis Dimitrios , Malli Foteini , Kotsiou Ourania , Gourgoulianis Konstantinos I.
Published: April 2022

Background: SARS-CoV-2 vaccines have shown high efficacy in protecting against COVID-19, although the determinants of vaccine effectiveness and breakthrough rates are yet to be determined. We aimed at investigating several factors affecting the SARS-CoV-2 IgG Spike (S) antibody responses on admission and clinical outcomes of COVID-19 disease in fully vaccinated, hospitalized patients. Methods: 102 subjects were enrolled in the study. Blood serum samples were collected from each patient upon admission for the semiquantitative determination of the SARS-CoV-2 IgG S levels with lateral flow assays. Factors influencing vaccine responses were documented. Results: 27 subjects had a negative antibody test upon hospital admission. Out of the 102 patients admitted to the hospital, 88 were discharged and 14 died. Both the absence of anti-S SARS-CoV-2 antibodies and poor clinical outcomes of COVID-19 disease were associated with older age, lower Ct values, and a shorter period between symptom onset and hospital admission. Ct values and time between symptom onset and hospitalization were independently associated with SARS-CoV-2 IgG S responses upon admission. The PaO2/FiO2 ratio was identified as an independent predictor of in-hospital mortality. Conclusions: Host- and disease-associated factors can predict SARS-CoV-2 IgG S responses and mortality in hospitalized patients with breakthrough SARS-CoV-2 Infection.
Computer-Aided Diagnosis of Gastrointestinal Protruded Lesions Using Wireless Capsule Endoscopy: A Systematic Review and Diagnostic Test Accuracy Meta-Analysis
Authors: Kim Hye Jin , Gong Eun Jeong , Bang Chang Seok , Lee Jae Jun , Suk Ki Tae , Baik Gwang Ho
Published: April 2022

Background: Wireless capsule endoscopy allows the identification of small intestinal protruded lesions, such as polyps, tumors, or venous structures. However, reading wireless capsule endoscopy images or movies is time-consuming, and minute lesions are easy to miss. Computer-aided diagnosis (CAD) has been applied to improve the efficacy of the reading process of wireless capsule endoscopy images or movies. However, there are no studies that systematically determine the performance of CAD models in diagnosing gastrointestinal protruded lesions. Objective: The aim of this study was to evaluate the diagnostic performance of CAD models for gastrointestinal protruded lesions using wireless capsule endoscopic images. Methods: Core databases were searched for studies based on CAD models for the diagnosis of gastrointestinal protruded lesions using wireless capsule endoscopy, and data on diagnostic performance were presented. A systematic review and diagnostic test accuracy meta-analysis were performed. Results: Twelve studies were included. The pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of CAD models for the diagnosis of protruded lesions were 0.95 (95% confidence interval, 0.93–0.97), 0.89 (0.84–0.92), 0.91 (0.86–0.94), and 74 (43–126), respectively. Subgroup analyses showed robust results. Meta-regression found no source of heterogeneity. Publication bias was not detected. Conclusion: CAD models showed high performance for the optical diagnosis of gastrointestinal protruded lesions based on wireless capsule endoscopy.
Exercise Preferences and Benefits in Patients Hospitalized with COVID-19
Authors: Kontopoulou Sevasti , Daniil Zoe , Gourgoulianis Konstantinos I. , Kotsiou Ourania S.
Published: April 2022

Background: Obese people are at risk of becoming severely ill due to SARS-CoV-2. The exercise benefits on health have been emphasized. Aim: To investigate the correlation of obesity with the length of hospitalization, the pre- and post-hospitalization exercise preferences of COVID-19 patients, and the impact of pre-admission or post-hospitalization physical activity on dyspnea one month after hospitalization and recovery time. Methods: A telephone survey was conducted in patients hospitalized at the Respiratory Medicine Department, University of Thessaly, Greece, from November to December 2020. Results: Two-thirds of the patients were obese. Obesity was not associated with the hospitalization time. Two-thirds of the patients used to engage in physical activity before hospitalization. Males exercised in a higher percentage and more frequently than women before and after hospitalization. The methodical pre-hospitalization exercise was associated with lower levels of dyspnea one month after hospitalization. In-hospital weight loss, comorbidities, and dyspnea on admission independently predicted longer recovery time. Lockdown had boosted men’s desire to exercise than females who were negatively affected. Conclusions: Obesity is common in COVID-19 hospitalized patients. In-hospital weight loss, comorbidities, and dyspnea on admission predicted a longer post-hospitalization recovery time. The pre-hospitalization exercise was associated with less post-hospitalization dyspnea and recovery time.
Redevelopment of Brownfields for Cultural Use from ERDF Fund—The Case of Hungary between 2014 and 2020
Authors: Szabó Mariann , Bozsoki Fruzsina
Published: April 2022

In the current research we aim to analyse the public redevelopment projects financed in Hungary from the Territorial and Settlement Development OP between 2014 and 2020, with special focus on cultural use. Brownfield redevelopment is a major topic in an urban development context from an urban sustainability, circularity, and creative urban/regional development point of view. Within the examined period, 39% of the brownfield redevelopment projects have cultural ties. A detailed introduction of the cases highlights the importance of landscape-oriented spatial strategies, temporary use, and mixed land use options in redevelopment for long-term viability. The original function of redevelopment projects encompasses a wide range. We could find industrial brownfields from the 19th century to agro-food facilities from the soviet era, which proves that the allocation of ERDF funds for brownfield redevelopments helped the rehabilitation of those sites which are important in showcasing Hungarian history.
Business Closures and (Re)Openings in Real-Time Using Google Places: Proof of Concept
Authors: Rigobon Daniel E. , Duprey Thibaut , Kotlicki Artur , Schnattinger  Philip , Baharian Soheil , Hurd Thomas R.
Published: April 2022

We present a new estimation of business opening and closure rates using data from Google Places—the data set behind the Google Maps service. Our algorithm, through a bisection routine, counts the appearance and disappearance of “pins” that represent unique businesses. As a proof of concept, we compute business opening and closure rates for the city of Ottawa during the reopening phase of the COVID-19 pandemic in mid-2021. The lifting of restrictions coincides with a wave of re-entry of temporarily closed businesses, suggesting that government support may have facilitated the survival of hibernating businesses. Our entry estimates are validated by a survey of new businesses. This methodology allows policymakers to monitor business dynamics in quasi-real-time during rapidly unfolding crises.
Asymmetric Exchange Rate Pass-Through in Turkish Imports of Cocoa Beans
Authors: Durmaz Nazif , Kagochi John
Published: April 2022

The present paper uses asymmetric cointegration and error-correction modeling where a nonlinear adjustment of the exchange rate yields results that are different than those yielded by linear models. We study cocoa imports for Turkey with advanced ARDL and nonlinear ARDL frameworks. Our findings reveal that there is considerable asymmetry for the case of Turkish cocoa bean imports from Côte d’Ivoire. Compared with imports from Ghana, there are significant differences in Turkish importers’ preferences when choosing between the two cocoa bean providers. Our results provide support for the nonlinear adjustment of the real Turkish lira–US dollar exchange rate and a hint of imperfect rivalry in Turkish cocoa bean imports.
A Hybrid Metaheuristic for the Omnichannel Multiproduct Inventory Replenishment Problem
Authors: Lorenzo-Espejo Antonio , Muñuzuri Jesús , Guadix José , Escudero-Santana Alejandro
Published: April 2022

In the current paradigm for the retail industry, which is experiencing a rapid evolution, especially in textile companies, the generic problem of product allocation in a distribution and supply chain consisting of one main warehouse and several locations, belonging to different sales channels, is a challenge. The omnichannel replenishment process focuses on dynamically optimizing a shop or intermediate warehouse inventory for a wide range of products based on a forecast of sales, in order to fulfill the demand of all of the channels considered. In this context, the aims of this work were (a) to optimize inventory replenishment for multiple channels and products that are not perishable but devalue over time, and (b) to implement a methodology that combines the benefits of the Particle Swarm Optimization metaheuristic and Simulated Annealing. This study was carried out for different sales periods, channels and product configurations by performing a sensitivity analysis between the way new solutions are updated and the degree of intensification used in local search.
Perceived Risk as a Determinant of Propensity to Adopt Account Information Services under the EU Payment Services Directive 2
Authors: Rosati Pierangelo , Fox Grace , Cummins Mark , Lynn Theo
Published: April 2022

Globalisation, technological advances, liberalisation of financial markets, and changing consumer behaviour are transforming banking profoundly. Under the EU Payment Services Directive 2 (PSD2), incumbent banks must open up their data, processes, and business functionalities to customers and third parties including rivals. It is critical to understand consumer behaviour post-PSD2, and the potential impact of PSD2 on the functioning of the retail banking and financial services market. In this preliminary study of 244 consumers from six European countries, we explore the role of social influence, facilitating conditions, perceived risk, and effort and performance expectancy in order to unravel the determinants of consumers’ acceptance of account information services (AIS) as provisioned under PSD2, which provide consolidated bank account information for consumers with multiple bank accounts across multiple banking institutions. Our findings suggest that the competing influences of (a) positive perceptions such as social influence, facilitating conditions, and performance expectancy, and (b) negative perceptions related to risk, sway consumers’ intentions to adopt AIS.
Incentives for Palm Oil Smallholders in Mandatory Certification in Indonesia
Authors: Pramudya Eusebius Pantja , Wibowo Lukas Rumboko , Nurfatriani Fitri , Nawireja Iman Kasiman , Kurniasari Dewi Ratna , Hutabarat Sakti , Kadarusman Yohanes Berenika , Iswardhani Ananda Oemi , Rafik Rukaiyah
Published: April 2022

The Indonesian Sustainable Palm Oil (ISPO) is a mandatory certification for palm oil plantations based on compliance with Indonesia’s regulations. Its implementation has been slow, particularly for independent smallholders that face problems of complicated requirements, limited capacity, and limited funding. Meanwhile, limited incentives are in place, either in the form of premium prices, ease of regulation, or funding. This article aims to elaborate on the role of incentives and their options in supporting the acceleration of ISPO implementation to ensure and improve the market access of smallholders. It identifies ways to develop incentives to facilitate the acceleration of ISPO certification and alternative financing sources available to support this. The method of this research is based on qualitative methodology using a literature review, policy document analysis, and in-depth interviews with informants from the government and smallholders. The analysis of this article shows that incentives are needed in the form of funding, regulatory measures, technical assistance, promotion, and rewards for good practices to provide better facilitation and financial support for the regulatory compliance in the legal, managerial and financial aspects of the ISPO. These incentives target government and smallholders. Implications for enabling these incentives include the improvement of government coordination, improved understanding of challenges faced by smallholders, and adoption of innovative approaches to manage financial resources, which are crucial to facilitate smallholders’ capacity and organizational improvement.
Exploring the Contributions by Transportation Features to Urban Economy: An Experiment of a Scalable Tree-Boosting Algorithm with Big Data
Authors: Lee Changju , Lee Sunghoon
Published: April 2022

Previous studies regarding transportation impacts on economic development in urban areas have three major issues—the limited scope of analysis mostly with the change of property values, the exclusion of smart transportation systems as features despite their potential for urban areas, and stereotyped approaches with limited types of variables. To surmount such limitations, this research adopted the concept of Big Data with machine learning techniques. As such, a total of 67 features from main categories, including the change of business, geographical boundary, socio-economic, land value, transportation, smart transportation, sales, and floating population were analyzed with XGBoost and SHAP algorithms. Given that the rise and fall of business is a major consideration for economic development in urban areas, the change in the total number of sales was selected as a target value. As a result, sales-related features showed the largest contribution to the rise of business, among others. It was also noted that features related to smart transportation systems obviously affected the success of business, even more than traditional ones from transportation. It is thus expected that the findings from this research will provide insights for decision-makers and researchers to make customized policies for boosting economic development in urban areas that are a major part of the urban economy to achieve sustainability.
Community Acceptance of Nature-Based Solutions in the Delta of the Tordera River, Catalonia
Authors: Nóblega-Carriquiry Andrea , March Hug , Sauri David
Published: April 2022

Much has been debated regarding the environmental and economic aspects that conform the pillars of sustainability in nature-based solutions (NbSs). However, the social implications are lagging behind in both theory and practice. NbSs are not inherently socially and environmentally just and they might not work for or benefit everyone. On the contrary, they may lead to unequal environmental tradeoffs influencing therefore community acceptance. This research explored the different levels of community acceptance of NbSs in the Tordera delta (Catalonia) through structured interviews and Q-methodology with representative stakeholders. It pretended to contribute to more just NbS discussions by identifying variables of community acceptance through a socio-environmental perspective. The results exposed existing socio-economic and socio-spatial differences that cause unequal co-benefits and tradeoffs among stakeholders of the area. Three distinctive discourses were identified: (1) NbSs as an opportunity to re-naturalize the river; (2) the possibility of NbS implementation if aligned with the current socio-economic structure of the delta; and (3) the belief in a hybrid NbS future, combining grey infrastructure and NbSs. Building on those results and discussions, the paper reflected on a restructuration of the delta’s governance through further collaborative processes to seek a more socio-environmentally just and inclusive NbSs in the area.
A Review on Carbon Source and Sink in Arable Land Ecosystems
Authors: Liu Xiaochen , Wang Shuai , Zhuang Qianlai , Jin Xinxin , Bian Zhenxing , Zhou Mingyi , Meng Zhuo , Han Chunlan , Guo Xiaoyu , Jin Wenjuan , Zhang Yufei
Published: April 2022

Arable land ecosystems are among the most important terrestrial systems. The issues of carbon sequestration and emission reductions in arable land ecosystems have received extensive attention. Countries around the world have actively issued policies to manage arable land ecosystems. At present, more than 100 countries have made carbon neutralization target commitments. Various arable land management measures and arable land planting strategies have important impacts on the carbon storage of arable land ecosystems. Research on arable land carbon is of great significance to global climate change. This study attempts to investigate the problems and deficiencies in the current research by summarizing a number of studies, including the main methods for the quantitative research of carbon sources and sinks as well as the influencing factors in these ecosystems. In this study, it is found that due to the differences of climate patterns, soil properties and management practices in arable land ecosystems, the factors affecting carbon sources and sinks are of great heterogeneity and complexity. Generally, variations in natural factors affect the carbon balance in different regions, while human management measures, such as irrigation, fertilization and the degree of agricultural mechanization, are the leading factors causing changes to carbon sources and sinks in these ecosystems. In addition, there are still great uncertainties in the evaluation of carbon sources and sinks in these ecosystems caused by different estimation models and methods. Therefore, emphasis should be placed on model parameter acquisition and method optimization in the future. This review provides a scientific basis for understanding carbon sources and sinks in arable land ecosystems, enhancing their carbon sink capacity and guiding low-carbon agriculture on arable land.
Classifying New Hybrid Cooperation Models for Short Food-Supply Chains—Providing a Concept for Assessing Sustainability Transformation in the Urban-Rural Nexus
Authors: Martens Katrin , Rogga Sebastian , Zscheischler Jana , Pölling Bernd , Obersteg Andreas , Piorr Annette
Published: April 2022

In response to the negative effects caused by structures of the dominant agricultural system and new market opportunities, increasing food supply structures have re-emerged in the urban-rural context of industrialized countries in recent years. These food supply structures often accompany new forms of hybrid cooperation models, including actors and institutions that have not shared resources previously. They form new alliances for sustainable transformation in the agri-food sector. Simultaneously, discourse has arisen in science and practice about the sustainability potential of such hybrid cooperation, referring to a lack of critical systematization and the necessity for creating an assessment concept. From the latter, one could draw conclusions about the transformative potential of such cooperation models and their potential to serve as blueprints for other regions. In this conceptual paper, a classification approach derived from social enterprise literature is elaborated, extended, and evaluated, to design a classification of new hybrid cooperation models that allow comparisons between regions and are sensitive to their dynamics. We show in an application how the classification approach, considering the dimensions “actors”, “resources”, and “actions”, serves to discover patterns in the development of short food-supply chain practices, identifying individual transition paths and, thus, making statements about their sustainability and challenges.
Enhancing Rural Resilience in a Tea Town of China: Exploring Tea Farmers’ Knowledge Production for Tea Planting, Tea Processing and Tea Tasting
Authors: Lin Xudan , Zhu Hong , Yin Duo
Published: April 2022

Rural areas have undergone visible transformations in recent decades. It leads to some ecological problems. Enhancing rural resilience is necessary in the face of these changes. However, previous literature often ignored the roles of indigenous actors in this process. Consequently, we conduct participant observation and in-depth interviews to explore the process by which local farmer knowledge is produced in Fenghuang, a rural area that concentrates on the tea industry in China, and how this process contributes to the agriculture resilience of individual and rural areas. We find that local knowledge is a dynamic composition of daily practice highlighting the nature of adaptability in farmers’ pursuits. Such knowledge is found to be constructed, exchanged, and then reshaped into a new and heterogeneous form that involves a mix of scientific forces and local practices, building a solid basis for individual and rural resilience. In addition, both sustainable agriculture and successful market promotion can be achieved by knowledge production. In this way, the meaning of “place” is reconstrued, morphing from a barren and backward rural area to a green and unique land with idyllic beauty. This metamorphosis offers belongingness to tea farmers and imposes on them the responsibility to contribute their efforts to the land.
Derivation Method of Architectural Asset Value Enhancement Zones in South Korea
Authors: Shon Donghwa , Kim Seungbum , Byun Nahyang
Published: April 2022

In June 2014, South Korea enacted a law to systematically preserve and utilize architectural assets to strengthen national competitiveness through the enhancement of architectural culture. An architectural asset value enhancement zone (AAVE) can be designated for an area in which a unique spatial environment has been created, centered on excellent architectural assets or in which architectural assets are densely concentrated. However, five years after the law was promulgated, while 14 local governments had completed basic investigations of architectural assets, only three had been designated as AAVE zones (as of March 2020). This is because the criteria for non-Hanok architectural assets are unclear, making it difficult to specify the scope of designation. This study aims to present and verify a methodology for deriving more effective AAVE zones. After establishing the criteria for architectural asset candidates, densely populated areas across the country were identified using GIS. Subsequently, a methodology was derived to classify candidate areas for the enhancement zone, based on the locations of these densely populated areas and designated/registered cultural heritage sites. The effectiveness of the methodology was reviewed through an actual area analysis, which indicated that the methodology is highly applicable to AAVE zones.
The Early Effect of Black Land Protection Plan in Northeast China on Industrial Pollution Using Synthetic Control Method
Authors: Tang Zhipeng , Song Wenming , Zou Jialing
Published: April 2022

This study used relevant industrial pollution emission data collected between 2004 and 2020 in northeastern China. It utilized the synthetic control method (SCM) and used entire county-level areas within the scope of the typical black land protection as the experimental group. Thirty regions in China (excluding Tibet, Hong Kong, Macao, and Taiwan), including the three non-black land areas of Liaoning, Jilin, Heilongjiang, and Inner Mongolia, and the other 26 entire provinces were taken as the control group. We studied whether the Outline of Black Land Protection Plan in Northeast China (2017–2030) (BLPP) has reduced local industrial pollution emissions since it was issued in 2017. The study found that implementation of the BLPP reduced industrial wastewater and sulfur dioxide emissions in black land areas significantly. Between 2017 and 2020, local industrial wastewater production decreased by 29.3% compared to the period without implementation of the outline, while industrial sulfur dioxide decreased by 12%. These results remained robust under the placebo and difference-in-difference (DID) tests. This once again showed that implementation of the outline had a significant effect on reducing industrial pollutant emissions in the black land area of northeastern China.
Does Network Externality of Urban Agglomeration Benefit Urban Economic Growth—A Case Study of the Yangtze River Delta
Authors: Jiang Jinliang , Xu Zhensheng , Lu Jiayi , Sun Dongqi
Published: April 2022

Scholars have conducted a large number of empirical studies on agglomeration externalities and network externalities at the urban scale, but there are relatively few studies at the urban agglomeration scale. For the integrated development of the Yangtze River Delta (YRD), analyzing the impact of network externalities and agglomeration externalities on urban development can provide academic references for the integrated development of urban agglomerations. The results show that: (1) From 2000 to 2010, the average GDP growth rate of the cities in the YRD region showed a rapid growth trend but began to slow down after 2010, showing an outward spatial distribution pattern. (2) From 2000 to 2020, the growth rate of Shanghai’s investment in cities in the YRD showed a downward trend and an outward spatial diffusion. The growth rate of investment within the YRD showed a slowing trend from 2000 to 2015 and increased after 2015, showing a spatial distribution from northwest to southeast. From 2000 to 2020, the growth rate of investment from other cities in China to cities in the YRD showed a continuous upward trend, and spatially formed a distribution characteristic from northwest to southeast. (3) The growth of internal investment in the YRD and that of other cities across China can accelerate urban economic growth, and the growth of internal investment in the YRD has a greater role in promoting economic growth, indicating that the “agglomeration externalities” and “network externalities” at the urban agglomeration scale both can promote urban economic growth, but the effect of the “agglomeration externalities” within the urban agglomeration is more obvious. (4) The growth of investment in the core city Shanghai does not play a significant role in the long-term economic growth of cities in the region.
Galvanotactic Migration of Glioblastoma and Brain Metastases Cells
Authors: Lange Falko , Venus Jakob , Shams Esfand Abady Daria , Porath Katrin , Einsle Anne , Sellmann Tina , Neubert Valentin , Reichart Gesine , Linnebacher Michael , Köhling Rüdiger , Kirschstein Timo
Published: April 2022

Galvanotaxis, the migration along direct current electrical fields, may contribute to the invasion of brain cancer cells in the tumor-surrounding tissue. We hypothesized that pharmacological perturbation of the epidermal growth factor (EGF) receptor and downstream phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevent galvanotactic migration. In our study, patient-derived glioblastoma and brain metastases cells were exposed to direct current electrical field conditions. Velocity and direction of migration were estimated. To determine the effects of EGF receptor antagonist afatinib and AKT inhibitor capivasertib, assays of cell proliferation, apoptosis and immunoblot analyses were performed. Both inhibitors attenuated cell proliferation in a dose-dependent manner and induced apoptosis. We found that most of the glioblastoma cells migrated preferentially in an anodal direction, while brain metastases cells were unaffected by direct current stimulations. Afatinib presented only a mild attenuation of galvanotaxis. In contrast, capivasertib abolished the migration of glioblastoma cells without genetic alterations in the PI3K/AKT pathway, but not in cells harboring PTEN mutation. In these cells, an increase in the activation of ERK1/2 may in part substitute the inhibition of the AKT pathway. Overall, our data demonstrate that glioblastoma cells migrate in the electrical field and the PI3K/AKT pathway was found to be highly involved in galvanotaxis.
Musculoskeletal Modeling of the Wrist via a Multi Body Simulation
Authors: Eschweiler Jörg , Praster Maximilian , Quack Valentin , Michalik Roman , Hildebrand Frank , Rath Björn , Migliorini Filippo
Published: April 2022

In this study, three different musculoskeletal modeling approaches were compared to each other. The objective was to show the possibilities in the case of a simple mechanical model of the wrist, using a simple multi-body-simulation (MBS) model, and using a more complex and patient-specific adaptable wrist joint MBS model. Musculoskeletal modeling could be a useful alternative, which can be practiced as a non-invasive approach to investigate body motion and internal loads in a wide range of conditions. The goal of this study was the introduction of computer-based modelling of the physiological wrist with (MBS-) models focused on the muscle and joint forces acting on the wrist.
Epigenetic Regulation of Chondrocytes and Subchondral Bone in Osteoarthritis
Authors: Ball Hope C. , Alejo Andrew L. , Samson Trinity K. , Alejo Amanda M. , Safadi Fayez F.
Published: April 2022

The aim of this review is to provide an updated review of the epigenetic factors involved in the onset and development of osteoarthritis (OA). OA is a prevalent degenerative joint disease characterized by chronic inflammation, ectopic bone formation within the joint, and physical and proteolytic cartilage degradation which result in chronic pain and loss of mobility. At present, no disease-modifying therapeutics exist for the prevention or treatment of the disease. Research has identified several OA risk factors including mechanical stressors, physical activity, obesity, traumatic joint injury, genetic predisposition, and age. Recently, there has been increased interest in identifying epigenetic factors involved in the pathogenesis of OA. In this review, we detail several of these epigenetic modifications with known functions in the onset and progression of the disease. We also review current therapeutics targeting aberrant epigenetic regulation as potential options for preventive or therapeutic treatment.
Kinetic, Isotherm and Thermodynamic Aspects of Zn2+ Biosorption by Spirulina platensis: Optimization of Process Variables by Response Surface Methodology
Authors: Alharbi Nada K. , Al-Zaban Mayasar I. , Albarakaty Fawziah M. , Abdelwahab Sayed F. , Hassan Sedky H. A. , Fawzy Mustafa A.
Published: April 2022

The aim of this study was to assess the efficiency of Spirulina platensis for removing Zn2+ ions from the aqueous solutions. The optimized conditions of 4.48 g/L algal dose, pH of 6.62 and initial zinc concentration of 29.72 mg/L obtained by response surface methodology were employed for Zn2+ biosorption by S. platensis and up to 97.90% Zn2+ was removed, showing that there is a favorable harmony between the experimental data and model predictions. Different kinetic and equilibrium models were used to characterize the biosorption manner of Spirulina as a biosorbent. The kinetic manner of Zn2+ biosorption was well characterized by the pseudo-second-order, implying that the adsorption process is chemical in nature. The Langmuir and Dubinin–Radushkevich isotherm models were best fit to the equilibrium data. The maximum adsorption capacity of the Langmuir monolayer was 50.7 mg/g. Furthermore, the thermodynamic analysis revealed that Zn2+ biosorption was endothermic, spontaneous and feasible. As a result of biosorption process, FTIR, SEM, and EDX investigations indicated noticeable alterations in the algal biomass’s properties. Therefore, the dried Spirulina biomass has been shown to be cost-effective and efficient for removing the heavy metals, particularly zinc ions from wastewater, and the method is practicable, and environmentally acceptable.
A Spotlight on the Role of Radiomics and Machine-Learning Applications in the Management of Intracranial Meningiomas: A New Perspective in Neuro-Oncology: A Review
Authors: Brunasso Lara , Ferini Gianluca , Bonosi Lapo , Costanzo Roberta , Musso Sofia , Benigno Umberto E. , Gerardi Rosa M. , Giammalva Giuseppe R. , Paolini Federica , Umana Giuseppe E. , Graziano Francesca , Scalia Gianluca , Sturiale Carmelo L. , Di Bonaventura Rina , Iacopino Domenico G. , Maugeri Rosario
Published: April 2022

Background: In recent decades, the application of machine learning technologies to medical imaging has opened up new perspectives in neuro-oncology, in the so-called radiomics field. Radiomics offer new insight into glioma, aiding in clinical decision-making and patients’ prognosis evaluation. Although meningiomas represent the most common primary CNS tumor and the majority of them are benign and slow-growing tumors, a minor part of them show a more aggressive behavior with an increased proliferation rate and a tendency to recur. Therefore, their treatment may represent a challenge. Methods: According to PRISMA guidelines, a systematic literature review was performed. We included selected articles (meta-analysis, review, retrospective study, and case–control study) concerning the application of radiomics method in the preoperative diagnostic and prognostic algorithm, and planning for intracranial meningiomas. We also analyzed the contribution of radiomics in differentiating meningiomas from other CNS tumors with similar radiological features. Results: In the first research stage, 273 papers were identified. After a careful screening according to inclusion/exclusion criteria, 39 articles were included in this systematic review. Conclusions: Several preoperative features have been identified to increase preoperative intracranial meningioma assessment for guiding decision-making processes. The development of valid and reliable non-invasive diagnostic and prognostic modalities could have a significant clinical impact on meningioma treatment.
Photoacoustic Imaging in Biomedicine and Life Sciences
Authors: Neprokin Alexey , Broadway Christian , Myllylä Teemu , Bykov Alexander , Meglinski Igor
Published: April 2022

Photo-acoustic imaging, also known as opto-acoustic imaging, has become a widely popular modality for biomedical applications. This hybrid technique possesses the advantages of high optical contrast and high ultrasonic resolution. Due to the distinct optical absorption properties of tissue compartments and main chromophores, photo-acoustics is able to non-invasively observe structural and functional variations within biological tissues including oxygenation and deoxygenation, blood vessels and spatial melanin distribution. The detection of acoustic waves produced by a pulsed laser source yields a high scaling range, from organ level photo-acoustic tomography to sub-cellular or even molecular imaging. This review discusses significant novel technical solutions utilising photo-acoustics and their applications in the fields of biomedicine and life sciences.
End-Systolic Eccentricity Index Obtained by Enhanced Computed Tomography Is a Predictor of Pulmonary Vascular Resistance in Patients with Chronic Thromboembolic Pulmonary Hypertension
Authors: Tsutsumi Yoshinori , Adachi Shiro , Nakano Yoshihisa , Iwano Shingo , Abe Shinji , Kato Katsuhiko , Naganawa Shinji
Published: April 2022

The usefulness of the parameters of biventricular function simultaneously measured using enhanced multi-detector computed tomography (MDCT) pulmonary angiography in patients with chronic thromboembolic pulmonary hypertension (CTEPH) has not been clarified. This study aimed to verify the correlation between left and right ventricular (RV) parameters and pulmonary vascular resistance (PVR). Patients who underwent enhanced MDCT before diagnostic right heart catheterization at Nagoya University Hospital between October 2014 and April 2021 were enrolled. The correlation of biventricular function and volume parameters with PVR was assessed. Eighty patients were retrospectively analyzed. Patients’ mean age was 65 ± 13 years, mean PVR was 9.1 (range, 6.1–11.3) Wood units, and mean end-systolic eccentricity index (esEI) was 1.76 ± 0.50. RV end-systolic volume (ESV) (p = 0.007), RV cardiac output (CO) (p < 0.001), RV ejection fraction (p < 0.001), LV end-diastolic volume (EDV) (p < 0.001), left ventricular (LV) ESV (p = 0.006), LVCO (p < 0.001), end-diastolic EI (p < 0.001), and esEI (p < 0.001) were significantly correlated with PVR. The LVEDV (p = 0.001) and esEI (p < 0.009) were independent predictors of PVR. Systolic pulmonary arterial pressure (PAP) (p < 0.001), diastolic PAP (p < 0.001), mean PAP (p < 0.001), right atrial pressure (p < 0.023), and PVR (p < 0.001) were significantly higher in the high esEI group than in the low esEI group. The esEI was a simple predictor of CTEPH severity.
Zinc Oxide Nanoparticles and Their Biosynthesis: Overview
Authors: Al Jabri Hareb , Saleem Muhammad Hamzah , Rizwan Muhammad , Hussain Iqbal , Usman Kamal , Alsafran Mohammed
Published: April 2022

Zinc (Zn) is plant micronutrient, which is involved in many physiological functions, and an inadequate supply will reduce crop yields. Its deficiency is the widest spread micronutrient deficiency problem; almost all crops and calcareous, sandy soils, as well as peat soils and soils with high phosphorus and silicon content are expected to be deficient. In addition, Zn is essential for growth in animals, human beings, and plants; it is vital to crop nutrition as it is required in various enzymatic reactions, metabolic processes, and oxidation reduction reactions. Finally, there is a lot of attention on the Zn nanoparticles (NPs) due to our understanding of different forms of Zn, as well as its uptake and integration in the plants, which could be the primary step toward the larger use of NPs of Zn in agriculture. Nanotechnology application in agriculture has been increasing over recent years and constitutes a valuable tool in reaching the goal of sustainable food production worldwide. A wide array of nanomaterials has been used to develop strategies of delivery of bioactive compounds aimed at boosting the production and protection of crops. ZnO-NPs, a multifunctional material with distinct properties and their doped counterparts, were widely being studied in different fields of science. However, its application in environmental waste treatment and many other managements, such as remediation, is starting to gain attention due to its low cost and high productivity. Nano-agrochemicals are a combination of nanotechnology with agrochemicals that have resulted in nano-fertilizers, nano-herbicides, nano-fungicides, nano-pesticides, and nano-insecticides being developed. They have anti-bacterial, anti-fungal, anti-inflammatory, antioxidant, and optical capabilities. Green approaches using plants, fungi, bacteria, and algae have been implemented due to the high rate of harmful chemicals and severe situations used in the manufacturing of the NPs. This review summarizes the data on Zn interaction with plants and contributes towards the knowledge of Zn NPs and its impact on plants.
On the Importance of Temporal Information for Remaining Useful Life Prediction of Rolling Bearings Using a Random Forest Regressor
Authors: Bienefeld Christoph , Kirchner Eckhard , Vogt Andreas , Kacmar Marian
Published: April 2022

Rolling bearings are frequently subjected to high stresses within modern machines. To prevent bearing failures, the topics of condition monitoring and predictive maintenance have become increasingly relevant. In order to efficiently and reliably maintain rolling bearings in a predictive manner, an estimate of the remaining useful life (RUL) is of great interest. The RUL prediction quality achieved when using machine learning depends not only on the selection of the sensor data used for condition monitoring, but also on its preprocessing. In particular, the execution of so-called feature engineering has a major impact on prediction quality. Therefore, in this paper, various methods of feature engineering are presented based on rolling–bearing endurance tests and recorded structure-borne sound signals. The performance of these methods is evaluated in the context of a regression-based RUL model. Furthermore, the way in which the quality of RUL prediction can be significantly improved is demonstrated, by adding further processed, time-considering features.