bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of Life and Stress Management in Healthcare Professionals of a Dental Care Setting at a Teaching Hospital in Rome: Results of a Randomized Controlled Clinical Trial
Authors: Guerra Fabrizio , Corridore Denise , Peruzzo Margherita , Dorelli Barbara , Raimondi Lucrezia , Ndokaj Artnora , Mazur Marta , Ottolenghi Livia , Torre Giuseppe , Polimeni Antonella
Published: October 2022

In the healthcare environment, more and more people experience work-related stress. The Faculty of Medicine and Dentistry of Sapienza University of Rome, having observed the need to take care of healthcare professionals, has set itself the objective of providing useful tools such as additional and necessary personal protective equipment for healthcare professionals. Objective: To promote health through better management, skills, and the use of strategies and solutions to identify, decompress, and neutralize those responsible for work-related stress mechanisms in order to take care of those who care (CURARE CURANTES). Materials and Methods: A randomized controlled clinical trial was conducted. The participants were enrolled by three departments of the Department of Dental and Maxillofacial Sciences of Rome; in consideration of emotional involvement of health professionals who work there. A motivational program was offered. Results: There were 17 and 16 healthcare professionals in the intervention and control groups, respectively. Levels of the mental composite score (MCS) varied both in the pre–post phase of the intervention group (p = 0.002), and between the intervention group and control group in the post phase (p = 0.006). No significant differences were observed for the physical composite score (PCS). Similarly, there were no significant differences regarding the positivity scale (PS) and the two dimensions of work-related stress (job demand and decision latitude). Conclusion: This study demonstrates the efficacy of yoga training practiced directly in the workplace and wearing work clothes, entering the work context, not weighing further on the healthcare workload, and being a way to carry out physical activity even in those cases in which professionals do not have the time to do it in their free time.
Oxidative Stress Responses and Gene Transcription of Mice under Chronic-Exposure to 2,6-Dichlorobenzoquinone
Authors: Wu Wenjing , Liu Yingying , Li Chunze , Zhuo Fangyu , Xu Zexiong , Hong Huachang , Sun Hongjie , Huang Xianfeng , Yu Xinwei
Published: October 2022

2,6-Dichlorobenzoquinone (2,6-DCBQ), as an emerging disinfection by-production, was frequently detected and identified in the drinking water; however, limited information is available for the toxic effect of 2,6-DCBQ on mice. In the present study, adult mice were used to assess the impact of 2,6-DCBQ via measuring the responses of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), the key genes (Heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) and glutamate-L-cysteine ligase catalytic subunit (GCLC)) in the Nrf2-keap1 pathway, and lipid peroxidation (malonaldehyde, MDA). Our results clearly indicated that 2,6-DCBQ decreased the activities of SOD and CAT, repressed the transcriptional levels of key genes in Nrf2-keap1 pathway, further caused oxidative damage on mice. These results provided evidence for assessing the threat of 2,6-DCBQ on human.
Comparison of the Effects of Different Forms of Nutrition Education on Adolescent Male Soccer Players
Authors: Gao Ziyu , Wang Sicheng , Peng Lianlian , Sun Lei , Qiu Peng , Bai Bingyi , Zhang Qingqing , Wu Junyu , Zha Yu , Zhu Fenglin , Wang Qirong
Published: October 2022

The purpose of this study was to compare the educational effects on nutrition knowledge of two teaching methods targeting adolescent male soccer players through learning online from WeChat account articles (WeChat group) or taking classroom courses (classroom group). The study investigates whether such teaching methods can improve self-efficacy and nutrition knowledge for athletes. A total of 41 U15 (age 15) youth male soccer players, 21 in the classroom group and 20 in the WeChat group, participated in the experiment by receiving the same nutrition education separately for 12 weeks. An athlete nutrition KAP questionnaire and self-efficacy questionnaire were conducted before the intervention, immediately after the intervention, and 6 weeks and 12 weeks after the intervention. As a result, the nutritional knowledge score and the total score of the athlete nutrition KAP questionnaire in the classroom group increased significantly and were notably higher than those in the WeChat group. Self-efficacy scores improved significantly in both groups. In conclusion, the study showed that the level of nutritional knowledge of U15 male soccer players was mediocre, and both forms of nutrition education can significantly improve the level of nutritional knowledge and self-efficacy of the players. In comparison, the educational effect of classroom teaching is significantly greater and more consistent than that of learning from WeChat public articles.
Living Alone but Not Feeling Lonely: The Effect of Self-Concealment on Perceived Social Support of Youth Living Alone in China
Authors: Zhang Linran , Fan Xiaoyue , Yu Zhanyu
Published: October 2022

The current study explored the mechanism of self-concealment on perceived social support among youth living alone and tried to clarify the two mediating variables, which are “psychological needs met through internet gratification” and “social self-esteem”, by using the Self-Concealment Scale, the Psychological Needs met through Internet Gratification Scale, the Texas Social Behavior Inventory and the Perceived Social Support Scale. Four hundred thirty-three working youth living alone who have lived alone or shared no emotional intersection with others were chosen as participants in this study. The results showed that: (1) the correlation between self-concealment, perceived social support, psychological needs met via internet gratification and social self-esteem was significant; (2) self-concealment positively predicted perceived social support; (3) self-concealment indirectly predicted perceived social support through the chain mediating effect of “psychological needs met via internet gratification” and “social self-esteem”. These results indicated that the self-concealment of youth living alone had a predictive effect on the perceived social support. The mechanisms of this effect included the direct effect of self-concealment and indirect effect through “psychological needs met via internet gratification” and “social self-esteem”.
Equity Analysis of Repeated Cross-Sectional Survey Data on Mental Health Outcomes in Saskatchewan, Canada during COVID-19 Pandemic
Authors: Muhajarine Nazeem , Adeyinka Daniel A. , Pisolkar Vaidehi , Ahmed Md Sabbir , Kallio Natalie , Coomaran Vithusha , McIntosh Tom , Novik Nuelle , Jeffery Bonnie
Published: October 2022

This paper aims to understand the impact of COVID-19 on three mental health outcomes—anxiety, depression, and mental health service use. Specifically, whether the associations between social and economic variables and these outcomes are exacerbated or buffered among equity-seeking groups in Saskatchewan. We analyzed secondary datasets of Saskatchewan adults from population-based national surveys conducted by Mental Health Research Canada (MHRC) on three occasions: cycle 2 (August 2020), cycle 5 (February 2021), and cycle 7 (June 2021). We examined temporal changes in the prevalence of anxiety, depression, and service utilization. Using the responses from 577 respondents in cycle 5 dataset (as it coincides with the peak of 2nd wave), we performed multinomial logistic regression. The policy implications of the findings were explored empirically through a World Café approach with 30 service providers, service users and policy makers in the province. The prevalence of anxiety and depression remained steady but high. Mental health services were not accessed by many who need it. Participants reporting moderate or severe anxiety were more likely to be 30–49 years old, women, and immigrants who earned less than $20,000 annually. Immigrants with either college or technical education presented with a lesser risk of severe anxiety. Factors associated with moderate or severe depression were younger age (<50 years), low household income, as well as immigrants with lower levels of education. Racialized groups had a lower risk of severe depression if they were under 30 years. Students and retirees also had a lower risk of severe depression. Canadian-born residents were more likely to require mental health supports but were not accessing them, compared to immigrants. Our analysis suggests mental health outcomes and service utilization remain a problem in Saskatchewan, especially among equity-seeking groups. This study should help drive mental health service redesign towards a client-centred, integrated, and equity-driven system in Saskatchewan.
Symptom Structure of Depression in Older Adults on the Qinghai–Tibet Plateau: A Network Analysis
Authors: Eli Buzohre , Zhou Yueyue , Chen Yaru , Huang Xin , Liu Zhengkui
Published: October 2022

Previous studies have confirmed that depression among residents in high-altitude areas is more severe, and that depression may be more persistent and disabling in older adults. This study aims to identify the symptom structure of depression among older adults on the Qinghai–Tibet Plateau (the highest plateau in the world) from a network perspective. This cross-sectional study enrolled 507 older adults (ages 60–80 years old) from the Yushu Prefecture, which is on the Qinghai–Tibet Plateau, China. Depressive symptoms were self-reported using the shortened Center for Epidemiological Studies–Depression Scale (CES-D-10). Then, a Gaussian graphical model (GGM) of depression was developed. Poor sleep, fear, and hopelessness about the future exhibited high centrality in the network. The strongest edge connections emerged between unhappiness and hopelessness about the future, followed by hopelessness about the future and fear; hopelessness about the future and poor sleep; fear and unhappiness; and then poor sleep and unhappiness in the network. The findings of this current study add to the small body of literature on the network structure and complex relationships between depressive symptoms in older adults in high-altitude areas.
Incidence Characteristics and Histological Types of Head and Neck Cancer among Adults in Central Sudan: A Retrospective Study
Authors: Gebril Marwa Ahmed Balila , Mukhtar Wail Nuri Osman , Elhassan Moawia Mohammed Ali , Mahmoud Ibrahim
Published: October 2022

Head and neck cancers (HNCs) are prevalent in Sudan, but the reasons for this and the incidence of different types of HNCs are not well understood. A cross-sectional retrospective study was conducted to provide baseline data on the epidemiology of HNCs among patients treated at the National Cancer Institute (NCI) in central Sudan. All cancer cases from 2016 to 2020 were retrieved from the NCI records. Of the 9475 new cancer patients who were registered at the NCI during the study period, 1033 (11%) had HNCs, of whom 767 (74.2%) were adults. The mean age of the adult patients was 54.5 years (standard deviation 15.8) and 449 (58.5%) patients were male. The annual incidence in adults was 4/105 population. The most common HNC sites were the nasopharynx (25.3%), hypopharynx (22.8%), and oral cavity (22.2%). Carcinoma was the most common diagnosis (87.6%), followed by lymphoma (5.6%). Most patients’ tumors were at a locally advanced (22%) or metastatic stage (47%) of HNCs at the time of presentation. Further studies to identify risk factors for HNCs, particularly for the most prevalent types in central Sudan, are needed. In addition, Sudan requires capacity building for cancer, including a national cancer registry.
Evaluating the Resources and Environmental Carrying Capacity in Laos Using a Three-Dimensional Tetrahedron Model
Authors: Zheng Fangyu , Xiao Chiwei , You Zhen , Feng Zhiming
Published: October 2022

(1) Background: The quantitative evaluation and comprehensive measurement of resources and environmental carrying capacity (RECC) are key links in the study of RECC from classification to synthesis. Laos, as the only landlocked country of Mainland Southeast Asia (MSEA), is an important economic corridor (i.e., China-MSEA Economic Corridor) of the Belt and Road Initiative (BRI). (2) Methods: Based on the human settlements index (HSI), resource carrying index (RCI), and socio-economic development index (SDI), here, a three-dimensional tetrahedron model for the comprehensive assessment of RECC with equilibrium significance was constructed, including HSI-based suitability classification, RCI-based restrictive classification, and SDI-based adaptability classification. Taking provinces as the basic unit, we quantitatively assessed and comprehensively evaluated RECC in Laos using a three-dimensional tetrahedron model. (3) Results: The human settlement environment in Laos is mainly characterized by the moderate suitable category (85%), while the high suitability area (merely 5%) supports more than 30% of the total population. Laos had over 90% of its area in good condition in resources and environmental carrying status (surplus or balanced state), translating into more than 95% of the population. The social and economic development level is mainly characterized by low-level development (43%), with nearly 30% of the population living in these low-level areas. The comprehensive bearing state of resources and environment is characterized by surplus, and 85% of the population is distributed in the surplus area, which occupies 63% of the land. (4) Conclusions: It is possible to better explore the adaptation strategies and countermeasures for enhancing RECC in Laos and provide a scientific reference for regional sustainable development. We believe that the three-dimensional tetrahedron method can be applied to quantitatively evaluate and comprehensively measure RECC at larger scale, e.g., the BRI regions.
Individuals with Sickle Cell Disease Using SBAR as a Communication Tool: A Pilot Study
Authors: Jean-Baptiste Deborah M. , Wassef Maureen , Bolyai Susan Sullivan , Jenerette Coretta
Published: October 2022

Background: Sickle cell disease (SCD) is a hemoglobinopathy that causes debilitating pain. Patients often report dissatisfaction during care seeking for pain or a sickle cell crisis (SCC). The Theory of Self-Care Management for SCD conceptualizes assertive communication as a self-care management resource that improves healthcare outcomes. Objectives: This pilot study aimed to determine whether adults with SCD could learn to use the Situation, Background, Assessment, Recommendation (SBAR) communication method using a web-based trainer, and it aimed to determine their perceptions of the training. Methods: The participants included n = 18 adults with SCD. Inter-rater reliability (IRR) among three reviewers was used to evaluate the participants’ ability to respond as expected to prompts using SBAR communication within the web-based platform. Content analysis was used to describe the participants’ perspectives of the acceptability of using the SBAR patient–HCP communication simulation. Results: The SBAR IRR ranged from 64 to 94%, with 72% to 94% of the responses being evaluated as the using of the SBAR component as expected. The predominant themes identified were (1) Patient–Provider Communication and Interaction; (2) Patients want to be Heard and Believed; (3) Accuracy of the ED Experience and Incorporating the Uniqueness of each Patient; and (4) the Overall Usefulness of the Video Trainer emerging. Conclusions: This pilot study supported the usefulness and acceptability of a web-based intervention in training adults with SCD to use SBAR to enhance patient–HCP communication. Enhancing communication may mitigate the barriers that individuals with SCD encounter during care seeking and improve the outcomes. Additional studies with larger samples need to be conducted.
Geochemical Fractionation and Source Identification of Pb and Cd in Riparian Soils and River Sediments from Three Lower Reaches Located in the Pearl River Delta
Authors: Xie Shaowen , Liu Chengshuai , He Bin , Chen Manjia , Gao Ting , Wei Xinghu , Liu Yuhui , Xia Yafei , Sun Qianying
Published: October 2022

Pb and Cd accumulation in riparian soils and river sediments in river basins is a challenging pollution issue due to the persistence and bioaccumulation of these two trace metals. Understanding the migration characteristics and input sources of these metals is the key to preventing metal pollution. This study was conducted to explore the contents, geochemical fractionation, and input sources of Pb and Cd in riparian soils and river sediments from three lower reaches of the Pearl River Delta located in the Guangdong–Hong Kong–Macao Greater Bay Area. The total concentration of all Pb and Cd values exceeded the background values to varying degrees, and the exchangeable fraction of Cd in riparian soils and river sediments accounted for the largest proportion, while that of Pb was dominated by the residual fraction. Geoaccumulation index calculations showed that in the riparian soils, the average accumulation degree of Pb (0.52) in the Beijiang River (BJR) was the highest, while that of Cd (2.04) in the Xijiang River (XJR) was the highest. Unlike that in riparian soils, the maximum accumulation of Pb (0.76) and Cd (3.01) in river sediments both occurred in the BJR. Furthermore, the enrichment factor results also showed that Pb and Cd in the riparian soils and river sediments along the BJR were higher than those in the XJR and Dongjiang River (DJR). The relationship between enrichment factors and nonresidual fractions further proved that the enrichment factors of Cd were significantly correlated with the nonresidual fractions of Cd, which may imply various anthropogenic sources of Cd in the three reaches. Moreover, source identification based on principal component analysis (PCA) and Pb isotope ratio analysis indicated that riparian soils and river sediments have inconsistent pollution source structures. The PCA results showed that Pb and Cd were homologous inputs in the DJR, and there were significant differences only in the riparian soils and river sediments. Pb isotope tracing results further showed that the bedrock of high geological background from upstream may be the main reason for Cd accumulation in the XJR. However, the ultrahigh accumulation of Cd in the BJR is mainly caused by the input of the upstream mining and metallurgy industry. The control of upstream input sources will be the key to the prevention of trace metal pollution in these regions.
The Triple Burden of Tuberculosis, Human Immunodeficiency Virus and Silicosis among Artisanal and Small-Scale Miners in Zimbabwe
Authors: Moyo Dingani , Ncube Ronald , Kavenga Fungai , Chikwava Lilian , Mapuranga Tawanda , Chiboyiwa Nathan , Chimunhu Chipo , Mudzingwa Frank , Muzvidziwa Orippa , Ncube Petronella , Mando Tariro Christwish , Moyo Florence , Chigaraza Blessings , Masvingo Hellen , Timire Collins
Published: October 2022

Artisanal and small-scale mining is characterized by an excessive exposure to silica-containing dust, overcrowding, poor living conditions and limited access to primary health services. This poses a risk to tuberculosis, HIV infection and silicosis. The main purpose of the study is to evaluate the burden of tuberculosis, HIV and silicosis among artisanal and small-scale miners. We conducted a cross sectional study on 3821 artisanal and small-scale miners. We found a high burden of silicosis (19%), tuberculosis (6.8%) and HIV (18%) in a relatively young population, with the mean age of 35.5 years. Men were 1.8 times more likely to be diagnosed with silicosis compared to women, adjusted prevalence ratio [aPR = 1.75 (95% CI: 1.02–2.74)]. Artisanal and small-scale miners who were living with HIV were 1.25 times more likely to be diagnosed with silicosis compared to those who were negative, [aPR = 1.25 (1.00–1.57)]. The risk of silicosis increased with both duration as a miner and severity of exposure to silica dust. The risk of tuberculosis increased with the duration as a miner. Zimbabwe is currently experiencing a high burden of TB, silicosis and HIV among artisanal and small-scale miners. Multi-sectoral and innovative interventions are required to stem this triple epidemic in Zimbabwe.
The Impact of County Medical Community Reform on the Medical Service Efficiency of County-Level Public General Hospitals in China: A Case Study of Shanxi Province
Authors: Ye Yun , Evans Richard , Jing Li , Rizwan Muhammad , Xuan Yan , Lu Wei
Published: October 2022

China introduced the county medical community (CMC) reform, aimed to provide high-quality medical resources to rural citizens, in 2017. This study examines the impact of the reform on the medical service efficiency of county-level public general hospitals in Shanxi Province, China. In total, 92 county-level public general hospitals from Shanxi Province were taken as the research objective, and the super-efficiency SBM-DEA model was applied to measure medical service efficiency. Further, a two-way fixed-effect model was used to evaluate the impact of CMC reform on the medical service efficiency of county-level public general hospitals by using health statistics data from 2014 to 2018. The study reveals that the CMC reform improved the medical service efficiency of county-level public general hospitals by 15.6%. Moreover, the CMC reform had regional heterogeneity in its impact on the medical service efficiency of county-level public general hospitals. The CMC reform improved the medical service efficiency of hospitals in the southern region more than in the northern region of the province. The medical service efficiency of hospitals in the central region was also improved by CMC reform, but the causal relationship was not found significant. Further, hospital-level factors (e.g., fixed assets, hospital stay, and regional health center) and environmental factors (e.g., GDP, population, urbanization rate, and government subsidies) affected the medical service efficiency of county-level public hospitals during the process of promoting the CMC reform.
How Has COVID-19 Impacted Our Language Use?
Authors: Pisano Francesca , Manfredini Alessio , Brachi Daniela , Landi Luana , Sorrentino Lucia , Bottone Marianna , Incoccia Chiara , Marangolo Paola
Published: October 2022

The COVID-19 pandemic has led to severe consequences for people’s mental health. The pandemic has also influenced our language use, shaping our word formation habits. The overuse of new metaphorical meanings has received particular attention from the media. Here, we wanted to investigate whether these metaphors have led to the formation of new semantic associations in memory. A sample of 120 university students was asked to decide whether a target word was or was not related to a prime stimulus. Responses for pandemic pairs in which the target referred to the newly acquired metaphorical meaning of the prime (i.e., “trench”—“hospital”) were compared to pre-existing semantically related pairs (i.e., “trench”—“soldier”) and neutral pairs (i.e., “trench”—“response”). Results revealed greater accuracy and faster response times for pandemic pairs than for semantic pairs and for semantic pairs compared to neutral ones. These findings suggest that the newly learned pandemic associations have created stronger semantic links in our memory compared to the pre-existing ones. Thus, this work confirms the adaptive nature of human language, and it underlines how the overuse of metaphors evoking dramatic images has been, in part, responsible for many psychological disorders still reported among people nowadays.
Dynamics of the Burlan and Pomacochas Lakes Using SAR Data in GEE, Machine Learning Classifiers, and Regression Methods
Authors: Gómez Fernández Darwin , Salas López Rolando , Rojas Briceño Nilton B. , Silva López Jhonsy O. , Oliva Manuel
Published: October 2022

Amazonas is a mountain region in Peru with high cloud cover, so using optical data in the analysis of surface changes of water bodies (such as the Burlan and Pomacochas lakes in Peru) is difficult, on the other hand, SAR images are suitable for the extraction of water bodies and delineation of contours. Therefore, in this research, to determine the surface changes of Burlan and Pomacochas lakes, we used Sentinel-1 A/B products to analyse the dynamics from 2014 to 2020, in addition to evaluating the procedure we performed a photogrammetric flight and compared the shapes and geometric attributes from each lake. For this, in Google Earth Engine (GEE), we processed 517 SAR images for each lake using the following algorithms: a classification and regression tree (CART), Random Forest (RF) and support vector machine (SVM).) 2021-02-10, then; the same value was validated by comparing the area and perimeter values obtained from a photogrammetric flight, and the classification of a SAR image of the same date. During the first months of the year, there were slight increases in the area and perimeter of each lake, influenced by the increase in rainfall in the area. CART and Random Forest obtained better results for image classification, and for regression analysis, Support Vector Regression (SVR) and Random Forest Regression (RFR) were a better fit to the data (higher R2), for Burlan and Pomacochas lakes, respectively. The shape of the lakes obtained by classification was similar to that of the photogrammetric flight. For 2021-02-10, for Burlan Lake, all 3 classifiers had area values between 42.48 and 43.53, RFR 44.47 and RPAS 45.63 hectares. For Pomacohas Lake, the 3 classifiers had area values between 414.23 and 434.89, SVR 411.89 and RPAS 429.09 hectares. Ultimately, we seek to provide a rapid methodology to classify SAR images into two categories and thus obtain the shape of water bodies and analyze their changes over short periods. A methodological scheme is also provided to perform a regression analysis in GC using five methods that can be replicated in different thematic areas.
Drug Repurposing for Cystic Fibrosis: Identification of Drugs That Induce CFTR-Independent Fluid Secretion in Nasal Organoids
Authors: Rodenburg Lisa W. , Delpiano Livia , Railean Violeta , Centeio Raquel , Pinto Madalena C. , Smits Shannon M. A. , van der Windt Isabelle S. , van Hugten Casper F. J. , van Beuningen Sam F. B. , Rodenburg Remco N. P. , van der Ent Cornelis K. , Amaral Margarida D. , Kunzelmann Karl , Gray Michael A. , Beekman Jeffrey M. , Amatngalim Gimano D.
Published: October 2022

Individuals with cystic fibrosis (CF) suffer from severe respiratory disease due to a genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which impairs airway epithelial ion and fluid secretion. New CFTR modulators that restore mutant CFTR function have been recently approved for a large group of people with CF (pwCF), but ~19% of pwCF cannot benefit from CFTR modulators Restoration of epithelial fluid secretion through non-CFTR pathways might be an effective treatment for all pwCF. Here, we developed a medium-throughput 384-well screening assay using nasal CF airway epithelial organoids, with the aim to repurpose FDA-approved drugs as modulators of non-CFTR-dependent epithelial fluid secretion. From a ~1400 FDA-approved drug library, we identified and validated 12 FDA-approved drugs that induced CFTR-independent fluid secretion. Among the hits were several cAMP-mediating drugs, including β2-adrenergic agonists. The hits displayed no effects on chloride conductance measured in the Ussing chamber, and fluid secretion was not affected by TMEM16A, as demonstrated by knockout (KO) experiments in primary nasal epithelial cells. Altogether, our results demonstrate the use of primary nasal airway cells for medium-scale drug screening, target validation with a highly efficient protocol for generating CRISPR-Cas9 KO cells and identification of compounds which induce fluid secretion in a CFTR- and TMEM16A-indepent manner.
Noninvasive Diagnostics of Renal Amyloidosis: Current State and Perspectives
Authors: Fedotov Sergei A. , Khrabrova Maria S. , Anpilova Anastasia O. , Dobronravov Vladimir A. , Rubel Aleksandr A.
Published: October 2022

Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis.
Comprehensive Identification and Analyses of the GRF Gene Family in the Whole-Genome of Four Juglandaceae Species
Authors: Zhang Zhongrong , Quan Shaowen , Niu Jianxin , Guo Caihua , Kang Chao , Liu Jinming , Yuan Xing
Published: October 2022

The GRF gene family plays an important role in plant growth and development as regulators involved in plant hormone signaling and metabolism. However, the Juglandaceae GRF gene family remains to be studied. Here, we identified 15, 15, 19, and 20 GRF genes in J. regia, C. illinoinensis, J. sigillata, and J. mandshurica, respectively. The phylogeny shows that the Juglandaceae family GRF is divided into two subfamilies, the ε-group and the non-ε-group, and that selection pressure analysis did not detect amino acid loci subject to positive selection pressure. In addition, we found that the duplications of the Juglandaceae family GRF genes were all segmental duplication events, and a total of 79 orthologous gene pairs and one paralogous homologous gene pair were identified in four Juglandaceae families. The Ka/KS ratios between these homologous gene pairs were further analyzed, and the Ka/KS values were all less than 1, indicating that purifying selection plays an important role in the evolution of the Juglandaceae family GRF genes. The codon bias of genes in the GRF family of Juglandaceae species is weak, and is affected by both natural selection pressure and base mutation, and translation selection plays a dominant role in the mutation pressure in codon usage. Finally, expression analysis showed that GRF genes play important roles in pecan embryo development and walnut male and female flower bud development, but with different expression patterns. In conclusion, this study will serve as a rich genetic resource for exploring the molecular mechanisms of flower bud differentiation and embryo development in Juglandaceae. In addition, this is the first study to report the GRF gene family in the Juglandaceae family; therefore, our study will provide guidance for future comparative and functional genomic studies of the GRF gene family in the Juglandaceae specie.
Integrated Analysis of Cytokine Profiles in Malaria Patients Discloses Selective Upregulation of TGF-β1, β3, and IL-9 in Mild Clinical Presentation
Authors: Ndoricyimpaye Ella Larissa , Van Snick Jacques , Niyoyita Jean de Dieu , Kanimba Philbert , Mbonimpa Jean Bosco , Rutayisire Robert , Rutayisire Réverien , Ndahindwa Vedaste , Cheou Paméla , Coutelier Jean Paul , Rujeni Nadine
Published: October 2022

The proper control of Plasmodium infection requires a finely balanced immune response. Here, we evaluated the implication of TGF-β1 and TGF-β3 in this process using novel monoclonal antibodies to measure their plasma concentrations in comparison with other cytokines and the expression of FOXP3 mRNA. Plasma cytokine levels were measured in 80 patients with severe anaemic malaria and 186 with a mild presentation using ELISA, and rtPCR was used to measure FOXP3 mRNA expression. While no mature TGF-β isoforms were detected in the plasma, the latent TGF-β1 and TGF-β3 were strongly upregulated in patients with mild malaria and nearly undetected in patients with severe disease. Similar selective upregulation in mild patients was observed for IL-9 and FOXP3 mRNA, while IL-7, IL-10, IL-17, and IL-27, although higher in mild cases, were also detected in severe disease. In contrast, a clearly skewed trend of severe cases towards higher pro-inflammatory (IL-6, IL-13, TNF-α) and Th1 (IFN-γ) responses was observed, which was associated with a higher level of parasitaemia as well as lower IgG and higher IgM responses. Together, these results suggest that the stimulation of regulatory T cells through TGF-β1/TGF-β3 and IL-9 is paramount to an effective and balanced protective immunity in natural human malaria infection.
Study of siRNA Delivery via Polymeric Nanoparticles in Combination with Angiogenesis Inhibitor for The Treatment of AFP-Related Liver Cancer
Authors: Punuch Kittiporn , Wongwan Chamaiphorn , Jantana Saranrat , Somboonyosdech Chayapol , Rodponthukwaji Kamonlatth , Kunwong Natsuda , Nguyen Kytai T. , Sirivatanauksorn Vorapan , Sirivatanauksorn Yongyut , Srisawat Chatchawan , Punnakitikashem Primana
Published: October 2022

Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (AFP-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The AFP siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of AFP-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. AFP-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that AFP-siRNA incorporated with NPs could significantly silence AFP-mRNA expression compared to unloaded NPs. Interestingly, the expression level of AFP-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.
Autoimmune Pancreatitis: From Pathogenesis to Treatment
Authors: Nista Enrico Celestino , De Lucia Sara Sofia , Manilla Vittoria , Schepis Tommaso , Pellegrino Antonio , Ojetti Veronica , Pignataro Giulia , Zileri dal Verme Lorenzo , Franceschi Francesco , Gasbarrini Antonio , Candelli Marcello
Published: October 2022

Autoimmune pancreatitis (AIP) is a rare disease. The diagnosis of AIP is difficult and should be made by a comprehensive evaluation of clinical, radiological, serological, and pathological findings. Two different types of AIP have been identified: autoimmune pancreatitis type 1 (AIP-1), which is considered a pancreatic manifestation of multiorgan disease related to IgG4, and autoimmune pancreatitis type 2 (AIP-2), which is considered a pancreas-specific disease not related to IgG4. Although the pathophysiological conditions seem to differ between type 1 and type 2 pancreatitis, both respond well to steroid medications. In this review, we focused on the pathogenesis of the disease to develop a tool that could facilitate diagnosis and lead to the discovery of new therapeutic strategies to combat autoimmune pancreatitis and its relapses. The standard therapy for AIP is oral administration of corticosteroids. Rituximab (RTX) has also been proposed for induction of remission and maintenance therapy in relapsing AIP-1. In selected patients, immunomodulators such as azathioprine are used to maintain remission. The strength of this review, compared with previous studies, is that it focuses on the clear difference between the two types of autoimmune pancreatitis with a clearly delineated and separate pathogenesis. In addition, the review also considers various therapeutic options, including biologic drugs, such as anti-tumor necrosis factor (TNF) therapy, a well-tolerated and effective second-line therapy for AIP type 2 relapses or steroid dependence. Other biologic therapies are also being explored that could provide a useful therapeutic alternative to corticosteroids and immunosuppressants, which are poorly tolerated due to significant side effects.
Quantitative Proteomic Analysis Reveals the Key Molecular Events Driving Phaeocystis globosa Bloom and Dissipation
Authors: Zhang Shu-Fei , Han Bei-Bei , Shi Rong-Jun , Wu Feng-Xia , Rao Yi-Yong , Dai Ming , Huang Hong-Hui
Published: October 2022

Phaeocystis globosa is a marine-bloom-forming haptophyte with a polymorphic life cycle alternating between free-living cells and a colonial morphotype, that produces high biomass and impacts ecological structure and function. The mechanisms of P. globosa bloom formation have been extensively studied, and various environmental factors are believed to trigger these events. However, little is known about the intrinsic biological processes that drive the bloom process, and the mechanisms underlying P. globosa bloom formation remain enigmatic. Here, we investigated a P. globosa bloom occurring along the Chinese coast and compared the proteomes of in situ P. globosa colonies from bloom and dissipation phases using a tandem mass tag (TMT)-based quantitative proteomic approach. Among the 5540 proteins identified, 191 and 109 proteins displayed higher abundances in the bloom and dissipation phases, respectively. The levels of proteins involved in photosynthesis, pigment metabolism, nitrogen metabolism, and matrix substrate biosynthesis were distinctly different between these two phases. Ambient nitrate is a key trigger of P. globosa bloom formation, while the enhanced light harvest and multiple inorganic carbon-concentrating mechanisms support the prosperousness of colonies in the bloom phase. Additionally, colonies in the bloom phase have greater carbon fixation potential, with more carbon and energy being fixed and flowing toward the colonial matrix biosynthesis. Our study revealed the key biological processes underlying P. globosa blooms and provides new insights into the mechanisms behind bloom formation.
Discovery of Mitophagy Inhibitors with Therapeutic Potential in Different Familial Amyotrophic Lateral Sclerosis Mutations
Authors: Maestro Ines , de la Ballina Laura R. , Porras Gracia , Corrochano Silvia , De Lago Eva , Simonsen Anne , Boya Patricia , Martinez Ana
Published: October 2022

Mitophagy is the selective degradation of mitochondria by autophagy. It promotes the turnover of mitochondria and prevents the accumulation of dysfunctional mitochondria, which can lead to cellular degeneration. Mitophagy is known to be altered in several pathological conditions, especially in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). We recently demonstrated an increase in autophagy flux in lymphoblasts from ALS patients bearing a mutation in SOD1. Thus, the identification of mitophagy inhibitors may be a therapeutic option to recover mitochondrial homeostasis. Here, using a phenotypic mitophagy assay, we identified a new mitophagy inhibitor, the small molecule named IGS2.7 from the MBC library. Interestingly, the treatment of different cellular and in vivo models of ALS with mutations on SOD1 and TARDBP with this inhibitor restores autophagy to control levels. These results point mitophagy inhibitors, especially IGS2.7, to a new therapeutic approach for familial ALS patients.
Macrophage Phenotypes and Gene Expression Patterns Are Unique in Naturally Occurring Metabolically Healthy Obesity
Authors: Ruggiero Alistaire D. , Vemuri Ravichandra , Block Masha , DeStephanis Darla , Davis Matthew , Chou Jeff , Williams Abigail , Brock Ashlynn , Das Swapan Kumar , Kavanagh Kylie
Published: October 2022

Obesity impacts 650 million individuals globally, often co-occurring with metabolic syndrome. Though many obese individuals experience metabolic abnormalities (metabolically unhealthy obese [MUO]), ~30% do not (metabolically healthy obese [MHO]). Conversely, >10% of lean individuals are metabolically unhealthy (MUL). To evaluate the physiologic drivers of these phenotypes, a 44-animal African green monkey cohort was selected using metabolic syndrome risk criteria to represent these four clinically defined health groups. Body composition imaging and subcutaneous adipose tissue (SQ AT) biopsies were collected. Differences in adipocyte size, macrophage subtype distribution, gene expression, vascularity and fibrosis were analyzed using digital immunohistopathology, unbiased RNA-seq, endothelial CD31, and Masson’s trichrome staining, respectively. MHO AT demonstrated significant increases in M2 macrophages (p = 0.02) and upregulation of fatty acid oxidation-related terms and transcripts, including FABP7 (p = 0.01). MUO AT demonstrated downregulation of these factors and co-occurring upregulation of immune responses. These changes occurred without differences in AT distributions, adipocyte size, AT endothelial cells, collagen I deposition, or circulating cytokine levels. Without unhealthy diet consumption, healthy obesity is defined by an increased SQ AT M2/M1 macrophage ratio and lipid handling gene expression. We highlight M2 macrophages and fatty acid oxidation as targets for improving metabolic health with obesity.
High-Molecular-Weight Dextran-Type Exopolysaccharide Produced by the Novel Apilactobacillus waqarii Improves Metabolic Syndrome: In Vitro and In Vivo Analyses
Authors: Ahmad Waqar , Boyajian Jacqueline L. , Abosalha Ahmed , Nasir Anam , Ashfaq Iram , Islam Paromita , Schaly Sabrina , Thareja Rahul , Hayat Azam , Rehman Mujaddad ur , Anwar Munir Ahmad , Prakash Satya
Published: October 2022

Metabolic syndrome is a leading medical concern that affects one billion people worldwide. Metabolic syndrome is defined by a clustering of risk factors that predispose an individual to cardiovascular disease, diabetes and stroke. In recent years, the apparent role of the gut microbiota in metabolic syndrome has drawn attention to microbiome-engineered therapeutics. Specifically, lactic acid bacteria (LAB) harbors beneficial metabolic characteristics, including the production of exopolysaccharides and other microbial byproducts. We recently isolated a novel fructophilic lactic acid bacterium (FLAB), Apilactobacillus waqarii strain HBW1, from honeybee gut and found it produces a dextran-type exopolysaccharide (EPS). The objective of this study was to explore the therapeutic potential of the new dextran in relation to metabolic syndrome. Findings revealed the dextran’s ability to improve the viability of damaged HT-29 intestinal epithelial cells and exhibit antioxidant properties. In vivo analyses demonstrated reductions in body weight gain and serum cholesterol levels in mice supplemented with the dextran, compared to control (5% and 17.2%, respectively). Additionally, blood glucose levels decreased by 16.26% following dextran supplementation, while increasing by 15.2% in non-treated mice. Overall, this study displays biotherapeutic potential of a novel EPS to improve metabolic syndrome and its individual components, warranting further investigation.
The Transcriptomic Landscape of Pediatric Astrocytoma
Authors: Hernández-Hernández Abrahan , López-Santaella Tayde , Torres-Caballero Aranxa , Serrato Amarantha , Torres-Flores Ulises , Montesinos-Valencia Diego , Chico-Ponce de León Fernando , González-Carranza Vicente , Torres-García Samuel , Rebollar-Vega Rosa , De la Rosa-Velázquez Inti Alberto , Ortiz Rosario , Pérez-Ramírez Monserrat , García-Hernández Normand , García-Méndez Antonio , Arenas-Huertero Francisco
Published: October 2022

Central nervous system tumors are the most common solid neoplasia during childhood and represent one of the leading causes of cancer-related mortality. Tumors arising from astrocytic cells (astrocytomas) are the most frequently diagnosed, and according to their histological and pathological characteristics, they are classified into four categories. However, an additional layer of molecular classification considering the DNA sequence of the tumorigenesis-associated genes IDH1/2 and H3F3A has recently been incorporated into the classification guidelines. Although mutations in H3F3A are found exclusively in a subtype of grade IV pediatric astrocytoma, mutations in IDH1/2 genes are very rare in children under 14 years of age. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied. However, there is scarce information on these profiles in pediatric populations considering the status of tumorigenesis-associated genes. Therefore, here we report the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing. We found several well-documented biological functions associated with the misregulated genes in the four grades of astrocytoma, as well as additional biological pathways. Among the four grades of astrocytoma, we found shared misregulated genes that could have implications in tumorigenesis. Finally, we identified a transcriptional signature for almost all grades of astrocytoma that could be used as a transcription-based identification method.
Synthesis, Biological Activity and Molecular Docking of Chimeric Peptides Targeting Opioid and NOP Receptors
Authors: Wtorek Karol , Ghidini Alessia , Gentilucci Luca , Adamska-Bartłomiejczyk Anna , Piekielna-Ciesielska Justyna , Ruzza Chiara , Sturaro Chiara , Calò Girolamo , Pieretti Stefano , Kluczyk Alicja , McDonald John , Lambert David G. , Janecka Anna
Published: October 2022

Recently, mixed opioid/NOP agonists came to the spotlight for their favorable functional profiles and promising outcomes in clinical trials as novel analgesics. This study reports on two novel chimeric peptides incorporating the fragment Tyr-c[D-Lys-Phe-Phe]Asp-NH2 (RP-170), a cyclic peptide with high affinity for µ and κ opioid receptors (or MOP and KOP, respectively), conjugated with the peptide Ac-RYYRIK-NH2, a known ligand of the nociceptin/orphanin FQ receptor (NOP), yielding RP-170-RYYRIK-NH2 (KW-495) and RP-170-Gly3-RYYRIK-NH2 (KW-496). In vitro, the chimeric KW-496 gained affinity for KOP, hence becoming a dual KOP/MOP agonist, while KW-495 behaved as a mixed MOP/NOP agonist with low nM affinity. Hence, KW-495 was selected for further in vivo experiments. Intrathecal administration of this peptide in mice elicited antinociceptive effects in the hot-plate test; this action was sensitive to both the universal opioid receptor antagonist naloxone and the selective NOP antagonist SB-612111. The rotarod test revealed that KW-495 administration did not alter the mice motor coordination performance. Computational studies have been conducted on the two chimeras to investigate the structural determinants at the basis of the experimental activities, including any role of the Gly3 spacer.