bluuebunny/crossref_metadata_2025 huggingface dataset:
Minimum Emissions Configuration of a Green Energy–Steel System: An Analytical Model
Authors: Digiesi Salvatore , Mummolo Giovanni , Vitti Micaela
Published: May 2022

The need to significantly reduce emissions from the steelmaking sector requires effective and ready-to-use technical solutions. With this aim, different decarbonization strategies have been investigated by both researchers and practitioners. To this concern, the most promising pathway is represented by the replacement of natural gas with pure hydrogen in the direct reduced iron (DRI) production process to feed an electric arc furnace (EAF). This solution allows to significantly reduce direct emissions of carbon dioxide from the DRI process but requires a significant amount of electricity to power electrolyzers adopted to produce hydrogen. The adoption of renewable electricity sources (green hydrogen) would reduce emissions by 95–100% compared to the blast furnace–basic oxygen furnace (BF–BOF) route. In this work, an analytical model for the identification of the minimum emission configuration of a green energy–steel system consisting of a secondary route supported by a DRI production process and a renewable energy conversion system is proposed. In the model, both technological features of the hydrogen steel plant and renewable energy production potential of the site where it is to be located are considered. Compared to previous studies, the novelty of this work consists of the joint modeling of a renewable energy system and a steel plant. This allows to optimize the overall system from an environmental point of view, considering the availability of green hydrogen as an inherent part of the model. Numerical experiments proved the effectiveness of the model proposed in evaluating the suitability of using green hydrogen in the steelmaking process. Depending on the characteristics of the site and the renewable energy conversion system adopted, decreases in emissions ranging from 60% to 91%, compared to the BF–BOF route, were observed for the green energy–steel system considered It was found that the environmental benefit of using hydrogen in the secondary route is strictly related to the national energy mix and to the electrolyzers’ technology. Depending on the reference context, it was found that there exists a maximum value of the emission factor from the national electricity grid below which is environmentally convenient to produce DRI by using only hydrogen. It was moreover found that the lower the electricity consumption of the electrolyzer, the higher the value assumed by the emission factor from the electricity grid, which makes the use of hydrogen convenient.
Exploring National Park Visitors’ Judgements from Social Media: The Case Study of Plitvice Lakes National Park
Authors: Sergiacomi Carlotta , Vuletić Dijana , Paletto Alessandro , Barbierato Elena , Fagarazzi Claudio
Published: May 2022

This study aims to conduct a survey of visitor reviews of the Plitvice Lakes National Park in Croatia to detect strengths and weaknesses of the park. In total, 15,673 reviews written in the period between 2007 and 2021 were scraped from the social media platform TripAdvisor. The research applies a comprehensive combination of multidimensional scaling, sentiment analysis, and natural language processing approaches to a sample area of international naturalistic interest. Analyzing the opinions of visitors, the authors identify: the main topics of interest related to the management of the park; and the strengths and weaknesses on the basis of definitely positive and decidedly negative reviews, respectively. The tested methodology is easily applicable for the analysis of different naturalistic contexts and protected areas, even in different countries, thanks to the use of translated reviews. The results obtained show that visitors to protected natural areas are not only interested in naturalistic and landscape aspects but also in issues such as accessibility and management of routes and visits.
The Addition of Biochar and Hyper-Thermal Inoculum Can Regulate the Fate of Heavy Metals Resistant Bacterial Communities during the Livestock Manure Composting
Authors: Zhang Qingjun , Zhu Tong , Xiao Qingxiang , An Ning
Published: May 2022

In the present investigation the effects of biochar and hyper-thermal inoculum on the heavy-metal-resistant bacteria (HMRB) during livestock manure composting were studied. An experiment was performed on composting livestock manure and wheat straw amended with biochar and hyper-thermal inoculum. Physicochemical properties, enzyme activity, heavy metals (HMs), and bacterial activities were monitored, and a comprehensive assessment was analyzed during the composting process. The results showed that the dominant phyla of Proteobacteria, Bacteroidota, Actinobacteriota, and Chloroflexi were enriched, but this was not the case with Firmicutes. The abundance of Galbibacter, Thermobifida, Sphaerobacter, and Actinomadura was significantly different in CT15 and BHCT15. In addition, this study showed that the selected factors are less correlated with HMRB compared with the CT group. Therefore, this study could provide new insights into the effect of biochar and hyper-thermal inoculum amendments on the fate of HMRB under HMs and high temperature stress during livestock manure composting.
Cod Liver Oil’s Encapsulation into Sodium Alginate/Lupin Protein Beads and Its Application in Functional Meatballs’ Preparation
Authors: Elsebaie Essam Mohamed , Kassem Mona Morgan , Mousa Mona Metwally , Basuony Mahmoud Abdelhakiem Mansour , Zeima Neveen M. , Essa Rowida Younis
Published: May 2022

Cod liver oil (CLO) is an essential source of healthy ω-3 fatty acids to be employed in functional meals. However, its autoxidation sensitivity, solubility, and odour present it as challenging to handle. Its encapsulation might mitigate these problems. This research studied using alginate/lupine protein as a wall material for CLO encapsulation as well as to characterise CLO microcapsules for their size, sphericity factor, encapsulation efficiency, morphology (scanning electron microscopy), in vitro release, and thermal stability. In this study, the oxidative stability, quality parameters, and sensory attributes of meatballs enriched with free CLOs and encapsulated CLOs throughout storage at 4 ± 1 °C for 16 days were assessed. The CLO microspheres had a homogeneous round shape, a diameter of 0.82 ± 0.06 mm, a sphericity factor of 0.092 ± 0.01, an encapsulation efficiency of 95.62% ± 1.13%, and an accumulative release rate of 87.10% after 270 min in the stimulated gastrointestinal conditions. Additionally, it was discovered that encapsulated oil was more stable than free CLOs to heat treatments (70–100 °C, 24 h). pH, thiobarbituric acid-reactive substances, peroxide value, conjugated dienes value, and carbonyl content of meatballs enriched with microencapsulated CLOs were significantly lower when compared to free CLOs and/or control samples. CLO microcapsules improved the sensory characteristics of meatballs throughout storage; however, meatballs directly containing CLOs were rejected. Thus, the viability of alginate/LPI complex microcapsules containing CLOs to enrich meat products subjected to storage with refrigeration could be indicated without any change in the characteristics.
Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis
Authors: Justice Cristina M. , Musolf Anthony M. , Cuellar Araceli , Lattanzi Wanda , Simeonov Emil , Kaneva Radka , Paschall Justin , Cunningham Michael , Wilkie Andrew O. M. , Wilson Alexander F. , Romitti Paul A. , Boyadjiev Simeon A.
Published: May 2022

Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.
Fracture Transmissivity in Prospective Host Rocks for Enhanced Geothermal Systems (EGS)
Authors: Herrmann Johannes , Schuster Valerian , Cheng Chaojie , Milsch Harald , Rybacki Erik
Published: May 2022

We experimentally determined the hydraulic properties of fractures within various rock types, focusing on a variety of Variscan rocks. Flow-through experiments were performed on slate, graywacke, quartzite, granite, natural fault gouge, and claystone samples containing an artificial fracture with a given roughness. For slate samples, the hydraulic transmissivity of the fractures was measured at confining pressures, pc, at up to 50 MPa, temperatures, T, between 25 and 100 °C, and differential stress, σ, acting perpendicular to the fracture surface of up to 45 MPa. Fracture transmissivity decreases non-linearly and irreversibly by about an order of magnitude with increasing confining pressure and differential stress, with a slightly stronger influence of pc than of σ. Increasing temperature reduces fracture transmissivity only at high confining pressures when the fracture aperture is already low. An increase in the fracture surface roughness by about three times yields an initial fracture transmissivity of almost one order of magnitude higher. Fractures with similar surface roughness display the highest initial transmissivity within slate, graywacke, quartzite and granite samples, whereas the transmissivity in claystone and granitic gouge material is up to several orders of magnitude lower. The reduction in transmissivity with increasing stress at room temperature varies with composition and uniaxial strength, where the deduction is lowest for rocks with a high fraction of strong minerals and associated high brittleness and strength. Microstructural investigations suggest that the reduction is induced by the compaction of the matrix and crushing of strong asperities. Our results suggest that for a given surface roughness, the fracture transmissivity of slate as an example of a target reservoir for unconventional EGS, is comparable to that of other hard rocks, e.g., granite, whereas highly altered and/or clay-bearing rocks display poor potential for extracting geothermal energy from discrete fractures.
Evaluating a Novel Extended Scope of Occupational Therapy Service Aimed at Hospital Avoidance in Tasmania, Australia, from the Perspective of Stakeholders
Authors: Van Dam Pieter Jan , Reid Leah , Elliott Sarah , Dwyer Mitchell
Published: May 2022

The Australian state of Tasmania has seen a spike in Emergency Department presentations in recent years, particularly among the elderly. A novel extended scope occupational therapy (ESOT) service was implemented by the Tasmanian Health Service, aimed at supporting hospital avoidance. Clients were referred to the ESOT service by other services after being assessed as having a high risk of imminent hospital presentation. Occupational Therapists provided short-term interventions related to falls, mobility, nutrition, and initiated onward referrals to other services. A convergent parallel mixed methods design was used to evaluate the ESOT service. Quantitative data from routinely collected administrative records and a purpose-built survey of referring clinicians were used alongside qualitative data from semi-structured interviews with clients/carers, to enable the triangulation of data. Quantitative data were analysed using descriptive statistics, while qualitative data collected in interviews were thematically analysed. A total of 104 extended scope interventions were provided to 100 clients. Most clients were able to stay at home. Qualitative data revealed that mobility, support, and facilitating access to support services were factors which added value to the client and carer experience. In conclusion, the ESOT program contributed to potentially avoiding hospital admissions and to improving the quality of life of participating clients.
Cognitive Training with Neurofeedback Using fNIRS Improves Cognitive Function in Older Adults
Authors: Acevedo Bianca P. , Dattatri Novia , Le Jennifer , Lappinga Claire , Collins Nancy L.
Published: May 2022

This study examined the effects of a 4-week cognitive training program with neurofeedback (CT-NF) among 86 healthy adults (M = 66.34 years, range 54–84) randomized to either a treatment (app-based ABC games) or control (Tetris) group. Participants completed seven cognitive assessments, pre- and post-intervention, and measured their cortical brain activity using a XB-01 functional near-infrared spectroscopy (fNIRS) brain sensor, while engaging in CT-NF. The treatment (ABC) group showed significant (pre/post-intervention) improvements in memory (MEM), verbal memory (VBM), and composite cognitive function, while the control group did not. However, both groups showed significant improvements in processing speed (PS) and executive function (EF). In line with other studies, we found that strength of cortical brain activity (measured during CT-NF) was associated with both cognitive (pre and post) and game performance. In sum, our findings suggest that CT-NF and specifically ABC exercises, confer improved cognition in the domains of MEM, VBM, PS, and EF.
Burnout Syndrome and Related Factors in Mexican Police Workforces
Authors: Torres-Vences Irene N. , Pérez-Campos Mayoral Eduardo , Mayoral Miguel , Pérez-Campos Eduardo Lorenzo , Martínez-Cruz Margarito , Torres-Bravo Iban , Alpuche Juan
Published: May 2022

Burnout (BO) is a response to prolonged exposure to work-related stressors characterized by emotional exhaustion (EE), depersonalization (DP), and reduced personal accomplishment (PA). The police working environment includes continued critical life-threatening situations, violence, and injuries, among other related factors putting them at high risk of distress. The objective of this study was to evaluate the association between Burnout Syndrome and sociodemographic, occupational, and health factors in Mexican police officers. We applied the Maslach Burnout Inventory Human Services Survey (MBI-HSS) to 351 active members of the Mexican police workforce. In addition, a specific questionnaire identified the presence of chronic degenerative diseases, hypertension, diabetes, digestive diseases, self-perception of food quality, and hours of sleep. Furthermore, 23.36% of police workforces presented high levels of burnout; 44.16% of police were highly emotionally exhausted, 49.29% had lost empathy with people, and 41.03% presented low personal achievement. Moreover, the worst levels of the syndrome were present in people with a poor self-perceived health status, poor perception of diet quality, without regular mealtimes, bad sleep habits, and elevated Body Mass Index. Data suggest that in Mexican police officers, BO is dimensionally different from all other groups previously studied (DP > EE > PA).
Stress-Inducing Factors vs. the Risk of Occupational Burnout in the Work of Nurses and Paramedics
Authors: Grochowska Aneta , Gawron Agata , Bodys-Cupak Iwona
Published: May 2022

Introduction: Contemporary healthcare faces new challenges and expectations from society. The profession of a nurse, as well as a paramedic, is essential for the efficient functioning of healthcare. It has its importance not only in promoting and preserving health but also in prevention. With the increasing importance of providing medical care at the highest level, it is expected of these two professional groups to have more knowledge and skills than a few years earlier. The daily contact with patients and their families, the low level of control of the environment, the hierarchical system of professional dependence, and the dissatisfaction with remuneration are becoming extremely burdensome aspects of the nursing and paramedic professions. Long-term exposure to stressors associated with these medical professions may, in the long term, lead to the emergence of occupational burnout syndrome. The aim of this study is an attempt to answer the question of whether and how stress factors affect the occurrence of occupational burnout in the work of nurses and paramedics working in various medical entities. Material and Methods: The study covered a group of 434 respondents, including 220 nurses and 214 paramedics, working professionally in hospital departments and care and treatment facilities as well as in hospital emergency departments and ambulance services. The study was carried out using a diagnostic survey based on the questionnaire technique using the authors’ questionnaire and the standardized MBI Ch. Maslach. Two statistical values were used to statistically analyze the research results and verify the adopted hypotheses: the chi-square test and the Student’s t-test. Results and Conclusions: The current study showed that the phenomenon of occupational burnout among the studied group affects only nurses, while this problem does not apply to the studied paramedics. The main stressor among the nurses and paramedics is, above all, a very high level of responsibility. Nurses are overburdened by excessive demands and shift work, while paramedics are mostly burdened by an excess of duties. Both nurses and paramedics claim that their work is often stressful, which leads to physical and mental exhaustion.
Can Financial Institutional Deepening and Renewable Energy Consumption Lower CO2 Emissions in G-10 Countries: Fresh Evidence from Advanced Methodologies
Authors: Mehmood Usman , Tariq Salman , Ul-Haq Zia , Agyekum Ephraim Bonah , Kamel Salah , Elnaggar Mohamed , Nawaz Hasan , Hameed Ammar , Ali Shafqat
Published: May 2022

To tackle the challenges associated with global warming and climate change, several countries set their targets to lower carbon emissions in accordance with COP21 (Paris Conference). Even though studies highlighted the different aspects that contribute to environmental degradation, there still exists the scarcity of adequate research that emphasizes the environmental implications of financial institutional deepening, renewable energy consumption (REC), and technology innovations. Therefore, this study investigated the significance of financial institutional deepening, REC, gross domestic product (GDP), imports, exports, and technology innovations to achieve sustainability in G-10 countries, namely The Netherlands, Germany, France, Switzerland, United Kingdom, Sweden, Japan, Belgium, Canada, and Italy from 1990 to 2020. The results obtained from cross-sectionally augmented autoregressive distributed lag (CS-ARDL) and the dynamic common correlated effects mean group (DCCEMG) models reveal that financial institutional deepening and imports positively impact CO2 emissions (CO2e) both in the long and short run. A 1% increase in financial institutional deepening and import will increase CO2e by 0.5403% and 0.2942% in the short run and 0.2980% and 0.1479% in the long run levels, respectively. Contrary to this, REC, GDP, exports, and technology innovations improve environmental quality in these countries. The Dumitrescu & Hurlin causality test shows bidirectional causality between imports and CO2e, GDP and CO2e, exports and CO2e, and financial institutional deepening and CO2e, compared to unidirectional causality from technology innovations to CO2e and from REC to CO2e. Apart from this, the outcomes suggest that policymakers in G-10 countries have to consider their financial markets and firms to revise their current environmental policies.
Predictive Models for Forecasting Public Health Scenarios: Practical Experiences Applied during the First Wave of the COVID-19 Pandemic
Authors: Martin-Moreno Jose M. , Alegre-Martinez Antoni , Martin-Gorgojo Victor , Alfonso-Sanchez Jose Luis , Torres Ferran , Pallares-Carratala Vicente
Published: May 2022

Background: Forecasting the behavior of epidemic outbreaks is vital in public health. This makes it possible to anticipate the planning and organization of the health system, as well as possible restrictive or preventive measures. During the COVID-19 pandemic, this need for prediction has been crucial. This paper attempts to characterize the alternative models that were applied in the first wave of this pandemic context, trying to shed light that could help to understand them for future practical applications. Methods: A systematic literature search was performed in standardized bibliographic repertoires, using keywords and Boolean operators to refine the findings, and selecting articles according to the main PRISMA 2020 statement recommendations. Results: After identifying models used throughout the first wave of this pandemic (between March and June 2020), we begin by examining standard data-driven epidemiological models, including studies applying models such as SIR (Susceptible-Infected-Recovered), SQUIDER, SEIR, time-dependent SIR, and other alternatives. For data-driven methods, we identify experiences using autoregressive integrated moving average (ARIMA), evolutionary genetic programming machine learning, short-term memory (LSTM), and global epidemic and mobility models. Conclusions: The COVID-19 pandemic has led to intensive and evolving use of alternative infectious disease prediction models. At this point it is not easy to decide which prediction method is the best in a generic way. Moreover, although models such as the LSTM emerge as remarkably versatile and useful, the practical applicability of the alternatives depends on the specific context of the underlying variable and on the information of the target to be prioritized. In addition, the robustness of the assessment is conditioned by heterogeneity in the quality of information sources and differences in the characteristics of disease control interventions. Further comprehensive comparison of the performance of models in comparable situations, assessing their predictive validity, is needed. This will help determine the most reliable and practical methods for application in future outbreaks and eventual pandemics.
Creative Intercorporeality in Collaborative Work of Choreographers with and without Disabilities: A Grounded Theory Approach
Authors: Kim Jian , Jin Jooyeon , Hong Aeryung
Published: May 2022

The purpose of this study was to present an academic discourse on a theoretical framework and acceptance process of ‘creative intercorporeality’ in the collaborative work of choreographers with and without disabilities. To this end, a grounded theory approach using a qualitative research method was employed to dancers who have participated in collaborative choreography. This study employed the perspective of social cognitive theory about the process in which dancers with and without disabilities form emotional empathy and trust relationships through continuous interactions for creative work. Physical, emotional, cognitive, and behavioral empathy and interactions in the collaborative work of choreographers with and without disabilities were discussed as a process of forming ‘creative intercorporeality’ that is defined as creative attitude and perspective consisting of harmony, concurrency, consistency, and balance.
Friendship in Later Life: How Friends Are Significant Resources in Older Persons’ Communication about Chronic Pain
Authors: Semlali Imane , Merminod Gilles , Weber Orest , Terrier Ana , Decosterd Isabelle , Rubli Truchard Eve , Singy Pascal
Published: May 2022

Background: This article focuses on how older persons perceive their friends’ role in their daily experience of chronic pain. It reports part of the results of a study in which we interviewed 49 participants, aged 75 and older, about the way they communicate about chronic pain within their social network. Methodology: Using discourse and content analysis, we first examine older persons’ definition of friendship, and then identify the various dimensions of friendship that are engaged in the communication about chronic pain. Results: Participants define close friends as people with whom they share intimacy and social proximity (same gender, age and experience of pain). These dimensions allow older persons to talk freely about their pain without the fear of being judged or rejected, particularly when it is related to a dynamic of reciprocity. Conclusions: This article shows that the contribution of friends to the everyday life of older persons with chronic pain is mainly that of providing emotional support.
Exploring the Evolution of the Accessibility of Educational Facilities and Its Influencing Factors in Mountainous Areas: A Case Study of the Rocky Desertification Area in Yunnan, Guangxi, and Guizhou
Authors: Yao Lingling , Lv Minjuan , Li Tao , Wang Donghua , Cao Xiaoshu
Published: May 2022

The optimal allocation of educational resources has been a hot issue, and exploring the accessibility of educational facilities in poor mountainous areas helps to reasonably plan the layout of educational facilities and promote the balanced development of education. Taking the rocky desertification area in Yunnan, Guangxi, and Guizhou (YGGRD) as the study area, based on the POI data of educational facilities in the YGGRD in 2000, 2010 and 2019, this study explored the evolution of the accessibility of educational facilities in the YGGRD through raster accessibility. And the influencing factors were analyzed by the ordinary least square method (OLS) and geographically weighted regression model (GWR), and evaluated the model through cross validation. The results show that the overall accessibility of educational facilities improved significantly from 2000 to 2019. Educational facilities mainly have good accessibility and average accessibility. Poor accessibility areas are concentrated in the interprovincial border regions, and the boundary effect is significant. County accessibility, population density and rural per capita disposable income have a great impact on the accessibility of educational facilities in the YGGRD. It is suggested to strengthen the construction of educational facilities in the interprovincial border regions, relocate and integrate villages, and improve the education quality of township schools to improve the supply of rural educational resources.
Ubiquitin and Ubiquitin-like Proteins in Cancer, Neurodegenerative Disorders, and Heart Diseases
Authors: Hwang Jin-Taek , Lee Ahyoung , Kho Changwon
Published: May 2022

Post-translational modification (PTM) is an essential mechanism for enhancing the functional diversity of proteins and adjusting their signaling networks. The reversible conjugation of ubiquitin (Ub) and ubiquitin-like proteins (Ubls) to cellular proteins is among the most prevalent PTM, which modulates various cellular and physiological processes by altering the activity, stability, localization, trafficking, or interaction networks of its target molecules. The Ub/Ubl modification is tightly regulated as a multi-step enzymatic process by enzymes specific to this family. There is growing evidence that the dysregulation of Ub/Ubl modifications is associated with various diseases, providing new targets for drug development. In this review, we summarize the recent progress in understanding the roles and therapeutic targets of the Ub and Ubl systems in the onset and progression of human diseases, including cancer, neurodegenerative disorders, and heart diseases.
The Social Norm of Hematopoietic Stem Cells and Dysregulation in Leukemia
Authors: Brown Geoffrey
Published: May 2022

The hematopoietic cell system is a complex ecosystem that meets the steady-state and emergency needs of the production of the mature blood cell types. Steady-state hematopoiesis replaces worn out cells, and the hematopoietic system is highly adaptive to needs during, for example, an infection or bleeding. Hematopoiesis is highly integrated and the cell hierarchy behaves in a highly social manner. The social tailoring of hematopoietic stem cells to needs includes the generation of cells that are biased towards a cell lineage; these cells remain versatile and can still adopt a different pathway having made a lineage “choice”, and some cytokines instruct the lineage fate of hematopoietic stem and progenitor cells. Leukemia stem cells, which may well often arise from the transformation of a hematopoietic stem cell, sustain the hierarchy of cells for leukemia. Unlike hematopoietic stem cells, the offspring of leukemia stem cells belongs to just one cell lineage. The human leukemias are classified by virtue of their differentiating or partially differentiating cells belonging to just one cell lineage. Some oncogenes set the fate of leukemia stem cells to a single lineage. Therefore, lineage restriction may be largely an attribute whereby leukemia stem cells escape from the normal cellular society. Additional antisocial behaviors are that leukemia cells destroy and alter bone marrow stromal niches, and they can create their own niches.
Characterization of a Cutibacterium acnes Camp Factor 1-Related Peptide as a New TLR-2 Modulator in In Vitro and Ex Vivo Models of Inflammation
Authors: Mayslich Constance , Grange Philippe Alain , Castela Mathieu , Marcelin Anne Geneviève , Calvez Vincent , Dupin Nicolas
Published: May 2022

Cutibacterium acnes (C. acnes) has been implicated in inflammatory acne where highly mutated Christie–Atkins–Munch–Petersen factor (CAMP)1 displays strong toll like receptor (TLR)-2 binding activity. Using specific antibodies, we showed that CAMP1 production was independent of C. acnes phylotype and involved in the induction of inflammation. We confirmed that TLR-2 bound both mutated and non-mutated recombinant CAMP1, and peptide array analysis showed that seven peptides (A14, A15, B1, B2, B3, C1 and C3) were involved in TLR-2 binding, located on the same side of the three-dimensional structure of CAMP1. Both mutated and non-mutated recombinant CAMP1 proteins induced the production of C-X-C motif chemokine ligand interleukin (CXCL)8/(IL)-8 in vitro in keratinocytes and that of granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF)-α, IL-1β and IL-10 in ex vivo human skin explants. Only A14, B1 and B2 inhibited the production of CXCL8/IL-8 by keratinocytes and that of (GM-CSF), TNF-α, IL-1β and IL-10 in human skin explants stimulated with rCAMP1 and C. acnes. Following pretreatment with B2, RNA sequencing on skin explants identified the 10 genes displaying the strongest differential expression as IL6, TNF, CXCL1, CXCL2, CXCL3, CXCL8, IL-1β, chemokine ligand (CCL)2, CCL4 and colony stimulating factor (CSF)2. We, thus, identified a new CAMP1-derived peptide as a TLR-2 modulator likely to be a good candidate for clinical evaluation.
High-Throughput In Vitro Screening Identified Nemadipine as a Novel Suppressor of Embryo Implantation
Authors: Chen Xian , Fernando Sudini Ranshaya , Lee Yin-Lau , Yeung William Shu-Biu , Ng Ernest Hung-Yu , Li Raymond Hang-Wun , Lee Kai-Fai
Published: May 2022

Current contraceptive methods interfere with folliculogenesis, fertilization, and embryo implantation by physical or hormonal approaches. Although hormonal contraceptive pills are effective in regulating egg formation, they are less effective in preventing embryo implantation. To explore the use of non-hormonal compounds that suppress embryo implantation, we established a high-throughput spheroid-endometrial epithelial cell co-culture assay to screen the Library of Pharmacologically Active Compounds (LOPAC) for compounds that affect trophoblastic spheroid (blastocyst surrogate) attachment onto endometrial epithelial Ishikawa cells. We identified 174 out of 1280 LOPAC that significantly suppressed BeWo spheroid attachment onto endometrial Ishikawa cells. Among the top 20 compounds, we found the one with the lowest cytotoxicity in Ishikawa cells, P11B5, which was later identified as Nemadipine-A. Nemadipine-A at 10 µM also suppressed BeWo spheroid attachment onto endometrial epithelial RL95-2 cells and primary human endometrial epithelial cells (hEECs) isolated from LH +7/8-day endometrial biopsies. Mice at 1.5 days post coitum (dpc) treated with a transcervical injection of 100 µg/kg Nemadipine-A or 500 µg/kg PRI-724 (control, Wnt-inhibitor), but not 10 µg/kg Nemadipine-A, suppressed embryo implantation compared with controls. The transcript expressions of endometrial receptivity markers, integrin αV (ITGAV) and mucin 1 (MUC1), but not β-catenin (CTNNB1), were significantly decreased at 2.5 dpc in the uterus of treated mice compared with controls. The reduction of embryo implantation by Nemadipine-A was likely mediated through suppressing endometrial receptivity molecules ITGAV and MUC1. Nemadipine-A is a potential novel non-hormonal compound for contraception.
Dissection of the Genetic Basis of Yield Traits in Line per se and Testcross Populations and Identification of Candidate Genes for Hybrid Performance in Maize
Authors: Ma Yuting , Li Dongdong , Xu Zhenxiang , Gu Riliang , Wang Pingxi , Fu Junjie , Wang Jianhua , Du Wanli , Zhang Hongwei
Published: May 2022

Dissecting the genetic basis of yield traits in hybrid populations and identifying the candidate genes are important for molecular crop breeding. In this study, a BC1F3:4 population, the line per se (LPS) population, was constructed by using elite inbred lines Zheng58 and PH4CV as the parental lines. The population was genotyped with 55,000 SNPs and testcrossed to Chang7-2 and PH6WC (two testers) to construct two testcross (TC) populations. The three populations were evaluated for hundred kernel weight (HKW) and yield per plant (YPP) in multiple environments. Marker–trait association analysis (MTA) identified 24 to 151 significant SNPs in the three populations. Comparison of the significant SNPs identified common and specific quantitative trait locus/loci (QTL) in the LPS and TC populations. Genetic feature analysis of these significant SNPs proved that these SNPs were associated with the tested traits and could be used to predict trait performance of both LPS and TC populations. RNA-seq analysis was performed using maize hybrid varieties and their parental lines, and differentially expressed genes (DEGs) between hybrid varieties and parental lines were identified. Comparison of the chromosome positions of DEGs with those of significant SNPs detected in the TC population identified potential candidate genes that might be related to hybrid performance. Combining RNA-seq analysis and MTA results identified candidate genes for hybrid performance, providing information that could be useful for maize hybrid breeding.
Lost by Transcription: Fork Failures, Elevated Expression, and Clinical Consequences Related to Deletions in Metastatic Colorectal Cancer
Authors: Smid Marcel , Wilting Saskia M. , Martens John W. M.
Published: May 2022

Among the structural variants observed in metastatic colorectal cancer (mCRC), deletions (DELs) show a size preference of ~10 kb–1 Mb and are often found in common fragile sites (CFSs). To gain more insight into the biology behind the occurrence of these specific DELs in mCRC, and their possible association with outcome, we here studied them in detail in metastatic lesions of 429 CRC patients using available whole-genome sequencing and corresponding RNA-seq data. Breakpoints of DELs within CFSs are significantly more often located between two consecutive replication origins compared to DELs outside CFSs. DELs are more frequently located at the midpoint of genes inside CFSs with duplications (DUPs) at the flanks of the genes. The median expression of genes inside CFSs was significantly higher than those of similarly-sized genes outside CFSs. Patients with high numbers of these specific DELs showed a shorter progression-free survival time on platinum-containing therapy. Taken together, we propose that the observed DEL/DUP patterns in expressed genes located in CFSs are consistent with a model of transcription-dependent double-fork failure, and, importantly, that the ability to overcome the resulting stalled replication forks decreases sensitivity to platinum-containing treatment, known to induce stalled replication forks as well. Therefore, we propose that our DEL score can be used as predictive biomarker for decreased sensitivity to platinum-containing treatment, which, upon validation, may augment future therapeutic choices.
Complex N-Linked Glycosylation: A Potential Modifier of Niemann–Pick Disease, Type C1 Pathology
Authors: Cawley Niamh X. , Lyons Anna T. , Abebe Daniel , Luke Rachel , Yerger Julia , Telese Rebecca , Wassif Christopher A. , Bailey-Wilson Joan E. , Porter Forbes D.
Published: May 2022

Complex asparagine-linked glycosylation plays key roles in cellular functions, including cellular signaling, protein stability, and immune response. Previously, we characterized the appearance of a complex asparagine-linked glycosylated form of lysosome-associated membrane protein 1 (LAMP1) in the cerebellum of Npc1−/− mice. This LAMP1 form was found on activated microglia, and its appearance correlated both spatially and temporally with cerebellar Purkinje neuron loss. To test the importance of complex asparagine-linked glycosylation in NPC1 pathology, we generated NPC1 knock-out mice deficient in MGAT5, a key Golgi-resident glycosyl transferase involved in complex asparagine-linked glycosylation. Our results show that Mgat5−/−:Npc1−/− mice were smaller than Mgat5+/+:Npc1−/− mice, and exhibited earlier NPC1 disease onset and reduced lifespan. Western blot and lectin binding analyses of cerebellar extracts confirmed the reduction in complex asparagine-linked glycosylation, and the absence of the hyper-glycosylated LAMP1 previously observed. Western blot analysis of cerebellar extracts demonstrated reduced calbindin staining in Mgat5−/−:Npc1−/− mice compared to Mgat5+/+:Npc1−/− mutant mice, and immunofluorescent staining of cerebellar sections indicated decreased levels of Purkinje neurons and increased astrogliosis in Mgat5−/−:Npc1−/− mice. Our results suggest that reduced asparagine-linked glycosylation increases NPC1 disease severity in mice, and leads to the hypothesis that mutations in genes involved in asparagine-linked glycosylation may contribute to disease severity progression in individuals with NPC1. To examine this with respect to MGAT5, we analyzed 111 NPC1 patients for two MGAT5 SNPs associated with multiple sclerosis; however, we did not identify an association with NPC1 phenotypic severity.
A Forward-Looking Approach to Compare Ranking Methods for Sports
Authors: Ochieng Peter Juma , London András , Krész Miklós
Published: May 2022

In this paper, we provide a simple forward-looking approach to compare rating methods with respect to their stability over time. Given a rating vector of entities involved in the comparison and a ranking indicated by the rating, the stability of the methods is measured by the change in rating vector and ranks of the entities over time from a forward-looking perspective. We investigate various linear algebraic rating methods and use the Euclidean distance and Kendall tau rank correlation to measure their stability in rating and ranking, respectively. The investigations are based on both rolling and expanding window approaches. We apply the methodology to sports as a widely known ranking and rating environment. The results suggest that PageRank and Massey rating methods provide better rating and ranking stability than simple methods, such as winning percentage, and more advanced ones, such as Colley’s least square and Keener’s eigenvector-based method. Finally, a simple way to examine the potential predictive power of the rating methods is also provided.
Significance of α-Myosin Heavy Chain (MYH6) Variants in Hypoplastic Left Heart Syndrome and Related Cardiovascular Diseases
Authors: Anfinson Melissa , Fitts Robert H. , Lough John W. , James Jeanne M. , Simpson Pippa M. , Handler Stephanie S. , Mitchell Michael E. , Tomita-Mitchell Aoy
Published: May 2022

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with complex genetic inheritance. HLHS segregates with other left ventricular outflow tract (LVOT) malformations in families, and can present as either an isolated phenotype or as a feature of a larger genetic disorder. The multifactorial etiology of HLHS makes it difficult to interpret the clinical significance of genetic variants. Specific genes have been implicated in HLHS, including rare, predicted damaging MYH6 variants that are present in >10% of HLHS patients, and which have been shown to be associated with decreased transplant-free survival in our previous studies. MYH6 (α-myosin heavy chain, α-MHC) variants have been reported in HLHS and numerous other CHDs, including LVOT malformations, and may provide a genetic link to these disorders. In this paper, we outline the MYH6 variants that have been identified, discuss how bioinformatic and functional studies can inform clinical decision making, and highlight the importance of genetic testing in HLHS.
A Comparison of Barrier Factors between Hospitals with and without Cardiac Rehabilitation Programs in Korea: A Nation-Wide Survey Research
Authors: Kim Chul , Sung Jidong , Han Jae-Young , Jee Sungju , Lee Jang Woo , Lee Jong Hwa , Kim Won-Seok , Bang Heui Je , Baek Sora , Joa Kyung-Lim , Kim Ae Ryoung , Lee So Young , Kim Jihee , Kim Chung Reen , Kwon Oh Pum
Published: May 2022

The percentage of patients undergoing cardiac rehabilitation programs (CRP) is very low (30–40%), and hospitals providing CRP are either insufficient or lacking, even in countries with advanced medical care; therefore, this study aims to investigate the barriers, as well as compare the differences between hospitals, with or without CRP. We conducted a survey, in which the questionnaire was distributed through post or email to 607 specialists who work at 164 hospitals performing percutaneous coronary interventions (PCI). The results were as follows: (1) of the 164 hospitals, 132 responded (response rate: 80.5%). While all 47 hospitals with CRP responded (100%), from among the 117 hospitals without CRP, 85 responded (72.7%). (2) Of the 607 specialists, 227 responded (response rate: 36.9%). The response rates according to specialties were as follows: cardiologists (28.9%), cardiac surgeons (24.5%), and physiatrists (64.1%). (3) While the specialists at hospitals with CRP identified patient referral, transportation, and cost as the major barriers, for those at hospitals without CRP, all items were considered barriers, especially the items related to equipment, space, workforce, and budget as being more serious barriers. Therefore, in order to actively promote CRP, it is suggested that governments consider the customized support system according to the performance of CRPs.
Impact of Intensive Care Unit Discharge Delay on Liver Transplantation Outcomes
Authors: Salimi Shirin , Pandya Keval , Davis Rebecca Jane , Crawford Michael , Pulitano Carlo , Strasser Simone Irene , McCaughan Geoffrey William , Majumdar Avik , Liu Ken
Published: May 2022

Background: For general intensive care unit (ICU) patients, ICU discharge delay (ICUDD) has been associated with an increased hospital length of stay (LOS) and the acquisition of multi-resistant organism (MRO) infections. The impact of ICUDD on liver transplant (LT) recipients is unknown. Methods: We retrospectively studied consecutive adult LT between 2011 and 2019. ICUDD was defined as >8 h between a patient being cleared for discharge to ward and the patient leaving the ICU. Results: 550 patients received LT and the majority (68.5%) experienced ICUDD. The median time between clearance for ward and the patient leaving the ICU was 25.6 h. No donor or recipient variables were associated with ICUDD. Patients cleared for discharge early in the week (Sunday-Tuesday) and those discharged outside routine work hours were more likely to experience ICUDD (p = 0.001 and p < 0.001, respectively). The median hospital LOS was identical (18 days, p = 0.96) and there were no differences in other patient outcomes. Patients who became colonized with MRO in the ICU spent a longer time there compared to those who remained MRO-free (9 vs. 6 days, p < 0.001); however, this was not due to ICUDD. Conclusion: ICUDD post-LT is common and does not prolong hospital LOS. ICUDD is not associated with adverse patient outcomes or MRO colonization.
The Association between Gestational Age and Risk for Long Term Ophthalmic Morbidities among Offspring Delivered in Different Preterm Subgroups
Authors: Tsumi Erez , Hazan Itai , Regev Tamir , Leeman Samuel , Barrett Chiya , Fried Regev Noa , Sheiner Eyal
Published: May 2022

Objective: To investigate whether there is a linear association between the degree of prematurity and the risk for long-term ophthalmic morbidity among preterm infants. Study design: A population-based, retrospective cohort study, which included all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. All infants were divided into four groups according to gestational age categories: extremely preterm births, very preterm births, moderate to late preterm births and term deliveries (reference group). Hospitalizations of offspring up to 18 years of age involving ophthalmic morbidity were evaluated. Survival curves compared cumulative hospitalizations and regression models controlled for confounding variables. Results: During the study period, 243,363 deliveries met the inclusion criteria. Ophthalmic-related hospitalization rates were lower among children born at term (0.9%) as compared with extremely preterm (3.6%), very preterm (2%), and moderate to late preterm (1.4%) born offspring (p < 0.01; using the chi-square test for trends). The survival curve demonstrated significantly different hospitalization rates between the gestational ages (p < 0.001). The regression demonstrated an independent risk for ophthalmic morbidity among extremely preterm born offspring (adjusted hazard ratio 3.8, confidence interval 1.6–9.2, p < 0.01), as well as very preterm and moderate to late preterm (adjusted hazard ratio 2.2 and 1.5, respectively) as compared with term deliveries. Conclusions: The risk for long-term ophthalmic-related hospitalization of preterm offspring gradually decreases as the gestational age increases.
Elimination of Defects in Mammograms Caused by a Malfunction of the Device Matrix
Authors: Tumakov Dmitrii , Kayumov Zufar , Zhumaniezov Alisher , Chikrin Dmitry , Galimyanov Diaz
Published: May 2022

Today, the processing and analysis of mammograms is quite an important field of medical image processing. Small defects in images can lead to false conclusions. This is especially true when the distortion occurs due to minor malfunctions in the equipment. In the present work, an algorithm for eliminating a defect is proposed, which includes a change in intensity on a mammogram and deteriorations in the contrast of individual areas. The algorithm consists of three stages. The first is the defect identification stage. The second involves improvement and equalization of the contrasts of different parts of the image outside the defect. The third involves restoration of the defect area via a combination of interpolation and an artificial neural network. The mammogram obtained as a result of applying the algorithm shows significantly better image quality and does not contain distortions caused by changes in brightness of the pixels. The resulting images are evaluated using Blind/Referenceless Image Spatial Quality Evaluator (BRISQUE) and Naturalness Image Quality Evaluator (NIQE) metrics. In total, 98 radiomics features are extracted from the original and obtained images, and conclusions are drawn about the minimum changes in features between the original image and the image obtained by the proposed algorithm.