bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic Conditions and Landowners’ Perception Affect the Intention to Restore Polylepis Forests in the Central Andes of Peru
Authors: Joseph Lunel , Yaranga Cano Raúl Marino , Arizapana-Almonacid Marco , Venelli Pyles Marcela , Freire de Siqueira Flávia , van den Berg Eduardo
Published: January 2021

Research Highlights: Families more dependent on crops as the main source of income of properties have a greater intention of restoring Polylepis forest areas. However, this intention reduces with the increase of family dependence on subsistence products supplied by Polylepis forests. Properties where the chances of restoration of Polylepis forests are greater are those where the educational and technical level is better. Objectives: We aimed to comprehend which socioeconomic factors of rural properties and families’ perception were determinant for the intention to restore Polylepis forests in the Central Andes region of Peru. Material and Methods: We collected data through visits and the application of questionnaires. We selected 13 rural communities in the Tulumayo River Basin. We randomly sampled 10 to 20 families in each community, depending on its size, totaling 200 families. We used generalized linear mixed model (GLMM) to test which variables affect the intention to restore the forest. Results: When crops are the main source of income in the property, the families have more intention to restore Polylepis areas, on the other hand, when Polylepis forests are an important source of products for the family subsistence, the intention to restore forests reduces, indicating that higher technological status has a positive impact on restoration. The perception that Polylepis forests are important for the existence of water sources had a positive impact on the families’ intention to restore the areas. However, the perception that Polylepis forests are important for native flora persistence had a negative impact on the intention to restore their areas. Conclusions: Our results showed that investment in improving the productivity of the properties and in the education of their landowners should increase the success of eventual programs for restoration of Polylepis forests.
Screening, Identification and Growth-Promotion Products of Multifunctional Bacteria in a Chinese Fir Plantation
Authors: Zhao Guangyu , Wei Yihui , Chen Jiaqi , Dong Yuhong , Hou Lingyu , Jiao Ruzhen
Published: January 2021

Purpose: This research was aimed to screen and identify multifunctional phosphorus-dissolving bacteria of a Chinese fir (Cunninghamia lanceolata) plantation and study its phosphorus-dissolving characteristics in order to provide strain resources and a theoretical basis for developing the appropriate bacterial fertilizer of a Chinese fir plantation. Methods: First, phosphorus-dissolving bacteria were isolated from the woodland soil of a Chinese fir plantation by Pikovskava inorganic phosphorus medium (PVK). Then, some growth-promoting indicators of primary screening strains were determined, including the capacity of phosphorus-solubilized, nitrogenase activity, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity, production of indole-3-acetic acid (IAA), secretion of iron carrier and so on. Finally, the screening multifunctional phosphorus-dissolving bacteria were identified, which were combined with colony characteristics, physiological and biochemical tests and molecular biotechnology. Results: (1) Thirteen phosphorus-dissolving bacteria were isolated and screened in total, and P5 (195.61 mg·L−1) had the strongest capacity of phosphorus-solubilized. Five phosphorus-dissolving bacteria were provided with nitrogenase activity, and the highest activity of nitrogenase was P10 and P5 (71.90 C2H4 nmol·mL−1·h−1 and 71.00 C2H4 nmol·mL−1·h−1, respectively). Four strains were provided with ACC deaminase activity, and the highest activity of ACC deaminase was P5 and P9, (0.74 μmol·mg−1·h−1 and 0.54 μmol·mg−1·h−1, respectively). Most strains could secrete IAA, and three strains of bacteria had a strong secretory ability, which could secrete IAA with a concentration greater than 15 mg·mL−1, and P5 was 18.00, P2 was 17.30, P6 was 15.59 (mg·mL−1). P5 produced carriers of iron better than others, and the ratio of the diameter of the iron production carrier ring to the diameter of the colony was 1.80, respectively, which was significantly higher than other strains. Combining all kinds of factors, P5 multifunctional phosphorus-dissolving bacteria were screened for eventual further study. (2) Strain P5 was identified as Burkholderia ubonensis, based on the colony characteristics, physiological and biochemical tests, 16SrDNA sequence analysis and phylogenetic tree construction. Conclusion: P5 has a variety of high-efficiency growth-promoting capabilities, and the ability to produce IAA, ACC deaminase activity and siderophore performance are significantly higher than other strains, which had great potential in the development of microbial fertilizer.
Acknowledgment to Reviewers of Forests in 2020
Authors:   Forests Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Forests maintains its standards for the high quality of its published papers [...]
Sensorial, Melissopalynological and Physico-Chemical Characteristics of Honey from Babors Kabylia’s Region (Algeria)
Authors: Ghorab Asma , Rodríguez-Flores María Shantal , Nakib Rifka , Escuredo Olga , Haderbache Latifa , Bekdouche Farid , Seijo María Carmen
Published: January 2021

This study aimed to characterize the honeys of Babors Kabylia through sensory, melissopalynological and physico-chemical parameters. Thirty samples of honey produced in this region were collected over a period of two years and analyzed. All the samples presented physico-chemical parameters in conformity with legislation on honey quality, with few exceptions, linked mainly to beekeeping management. The pollen spectrum revealed a great diversity with 96 pollen types. The main pollen types were spontaneous species as Fabaceae (Hedysarum, Trifolium, Genisteae plants), Asteraceae plants, Ericaceae (Erica arborea L.) or Myrtus and Pistacia. The sensory properties of samples showed a high tendency to crystallization, the colors were from white to brown, but most of them had gold color. Smell and odor corresponded mainly to vegetal and fruity families and in taste perceptions besides sweetness highlighted sourness and saltiness notes. Seventeen samples were polyfloral, one was from honeydew and twelve were monofloral from heather, genista plants, sulla, blackberry or Asteraceae. Heather and the honeydew samples showed the darkest color, the highest electrical conductivity and phenol and flavonoid content. A statistical analysis based on the most representative pollen types, sensory properties and some physico-chemical components allowed the differentiation of honey samples in terms of botanical origin.
Malignant Transformation of Heterotopic Pancreatic Tissue in a Patient with BRCA2 Mutation
Authors: Yeo Danson Xue Wei , Goh Nicholette , Chuah Khoon Leong , Amitbhai Sanghvi Kaushal , Oo Aung Myint , Ahmed Abdul Kareem Saleem , Nath Koura Aaryan
Published: January 2021

Background: Malignant transformation of heterotopic pancreatic tissue is a rare entity with only several case reports published in the scientific literature. Adjuvant chemotherapy following oncological resection for lesions with nodal metastasis has not been well described and there are no guidelines available to guide the management of these patients. Case Presentation: We present a case of gastric heterotopic pancreatic carcinoma with nodal metastasis in a young patient with breast cancer gene (BRCA) 2 mutation. He had undergone a laparoscopic wedge resection for a gastric lesion initially thought to be a gastrointestinal stroma tumor. Given the involvement of the wedge resection margins, the patient underwent a distal gastrectomy with oncological lymph nodal clearance. One out of the 33 harvested lymph nodes harboured micrometastasis while the main gastrectomy specimen did not have any residual malignancy. Following the histological diagnosis, he received an adjuvant chemotherapy regime akin to that prescribed for locally advanced pancreatic adenocarcinoma with good response. This is, to our knowledge, also the first such case report in a patient with BRCA2 mutation. Conclusions: Pre-operative diagnostic confirmation is challenging and endoscopic procedures pose significant false negatives. Reports of nodal metastasis following oncological resection are limited and there are no guidelines regarding adjuvant therapies. We would recommend a chemotherapy regimen similar to that for primary locally advanced pancreatic carcinoma in patients found to have nodal metastasis.
Linked-Read Whole Genome Sequencing Solves a Double DMD Gene Rearrangement
Authors: Onore Maria Elena , Torella Annalaura , Musacchia Francesco , D’Ambrosio Paola , Zanobio Mariateresa , Del Vecchio Blanco Francesca , Piluso Giulio , Nigro Vincenzo
Published: January 2021

Next generation sequencing (NGS) has changed our approach to diagnosis of genetic disorders. Nowadays, the most comprehensive application of NGS is whole genome sequencing (WGS) that is able to detect virtually all DNA variations. However, even after accurate WGS, many genetic conditions remain unsolved. This may be due to the current NGS protocols, based on DNA fragmentation and short reads. To overcome these limitations, we applied a linked-read sequencing technology that combines single-molecule barcoding with short-read WGS. We were able to assemble haplotypes and distinguish between alleles along the genome. As an exemplary case, we studied the case of a female carrier of X-linked muscular dystrophy with an unsolved genetic status. A deletion of exons 16–29 in DMD gene was responsible for the disease in her family, but she showed a normal dosage of these exons by Multiplex Ligation-dependent Probe Amplification (MLPA) and array CGH. This situation is usually considered compatible with a “non-carrier” status. Unexpectedly, the girl also showed an increased dosage of flanking exons 1–15 and 30–34. Using linked-read WGS, we were able to distinguish between the two X chromosomes. In the first allele, we found the 16–29 deletion, while the second allele showed a 1–34 duplication: in both cases, linked-read WGS correctly mapped the borders at single-nucleotide resolution. This duplication in trans apparently restored the normal dosage of exons 16–29 seen by quantitative assays. This had a dramatic impact in genetic counselling, by converting a non-carrier into a double carrier status prediction. We conclude that linked-read WGS should be considered as a valuable option to improve our understanding of unsolved genetic conditions.
A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks
Authors: Kehl Alexandra , Haaland Anita Haug , Langbein-Detsch Ines , Mueller Elisabeth
Published: January 2021

Hemophilia A is the most common coagulation factor disorder in humans and dogs. The disease is characterized by the lack or diminished activity of Factor VIII (FVIII), caused by variants in the F8 gene and inherited as an X chromosomal trait. Two related male Rhodesian Ridgebacks were diagnosed with Hemophilia A due to reduced FVIII activity. The purpose of the study was to determine the genetic cause and give breeding advice for the remaining family members in order to eradicate the variant. By Sanger sequencing a short interspersed nuclear element (SINE) insertion in exon 14 of the F8 gene was found. Perfect correlation of this genetic variant with clinical signs of hemophilia A in the family tree, and the lack of this genetic variant in more than 500 unrelated dogs of the same and other breeds, confirms the hypothesis of this SINE being the underlying genetic cause of Hemophilia A in this family. The identification of clinically unaffected female carriers allows subsequent exclusion of these animals from breeding, to avoid future production of clinically affected male offspring and more subclinical female carriers.
Post-Transcriptional Modifications of Conserved Nucleotides in the T-Loop of tRNA: A Tale of Functional Convergent Evolution
Authors: Roovers Martine , Droogmans Louis , Grosjean Henri
Published: January 2021

The high conservation of nucleotides of the T-loop, including their chemical identity, are hallmarks of tRNAs from organisms belonging to the three Domains of Life. These structural characteristics allow the T-loop to adopt a peculiar intraloop conformation able to interact specifically with other conserved residues of the D-loop, which ultimately folds the mature tRNA in a unique functional canonical L-shaped architecture. Paradoxically, despite the high conservation of modified nucleotides in the T-loop, enzymes catalyzing their formation depend mostly on the considered organism, attesting for an independent but convergent evolution of the post-transcriptional modification processes. The driving force behind this is the preservation of a native conformation of the tRNA elbow that underlies the various interactions of tRNA molecules with different cellular components.
The Influence of Social Support on the Relationship between Emotional Demands and Health of Hospital Nurses: A Cross-Sectional Study
Authors: Chang Hyoung Eun , Cho Sung-Hyun
Published: January 2021

Social support reduces the negative results of emotional labor. A more detailed analysis should be performed to facilitate adequate social support for nurses. Therefore, this study was conducted to examine the relationships among nurses’ emotional demands, social support, and health. A cross-sectional survey was conducted at two tertiary hospitals in South Korea. A sample of 117 nurses from eight units participated. Between-group differences in the main variables were analyzed using the t-test or Mann–Whitney test, and analysis of variance or the Kruskal–Wallis test. Nurses were classified into eight groups according to emotional demands and type of social support, and the effects of social support were analyzed based on mean scores. Greater social support from colleagues was associated with better health on all measures. However, greater social support from supervisors was associated with a higher incidence of burnout, stress, and sleeping troubles. Nurses’ high emotional demands must be managed actively by hospitals to maintain and promote their health. Providing appropriate social support with consideration of the nurse’s unit experience would help decrease the effects of emotional demands. Enhancing social support from nursing colleagues is a powerful way to manage the negative effects of nurses’ emotional demands.
Analysis of Policies Based on the Multi-Fuzzy Regression Discontinuity, in Terms of the Number of Deaths in the Coronavirus Epidemic
Authors: Wang Xianghui , Chen Chang , Du Yan , Zhang Yang , Wu Chengliang
Published: January 2021

It has been a year since the outbreak of the coronavirus epidemic 2019 (COVID-19). In the face of the global epidemic, governments in all countries have taken different prevention measures, such as social isolation, mandatory health protection, and the closure of schools and workplaces. The situation of the epidemic has clearly varied from country to country. In this context, research on the impact of policies for the control of the spread of the global epidemic is of great significance. In this paper, we examined data from a sample of 212 countries between 31 December 2019, and 21 May 2020, using multi-fuzzy regression discontinuity. We found that developed countries had relatively low sensitivity to the policy stringency index; however, policy control measures had a significant effect on epidemic control. In addition, the trend analysis showed that the corresponding management and control came into play only after the policy stringency index reached 50 or the policy management reached level II, and the robustness was optimal at this time. Therefore, the governments in all countries should realize that epidemic prevention and control are of great importance. They can strengthen policy stringency to control the spread of the epidemic, considering their national conditions in terms of the economy and health system.
The Association between Neighborhood Disorder and Health: Exploring the Moderating Role of Genotype and Marriage
Authors: Lei Man-Kit , Simons Ronald L.
Published: January 2021

The present study extends prior research on the link between neighborhood disorder and health by testing an integrated model that combines various social and biological factors. Hypotheses were tested using a sample of 325 African American women from the Family and Community Health Study (FACHS). As expected, inflammatory burden was the biophysiological mechanism that mediated much of the association between neighborhood physical disorder and perceived physical health. This finding provided additional support for the view that global self-ratings of health are powerful predictors of morbidity because, in large measure, they are indicators of chronic, systemic inflammation. Further, both genetic variation and marital status served to moderate the association between neighborhood disorder and health. Finally, being married largely eliminated the probability that neighborhood disorder would combine with genetic vulnerability to increase inflammatory burden and perceived illness. Overall, the findings demonstrate the value of constructing integrated models that specify various biophysiological mechanisms that link social conditions to physical health.
Age–Period–Cohort Analysis of Trends in Infectious Disease Mortality in South Korea from 1983 to 2017
Authors: Kim Hee Sook , Eun Sang Jun
Published: January 2021

We aimed to describe the infectious disease (ID) mortality trends and evaluate age–period–cohort (APC) effects on ID mortality in Korea. Using cause-of-death and census population estimates data from 1983–2017, age-standardized ID mortality trends were investigated by joinpoint regression analysis. The APC effects on ID mortality were estimated using intrinsic estimator models. The age effect showed a J-shaped concave upward curve. Old age, especially ≥70 years, was a critical factor for ID deaths. Similar to the W-shaped period curve, ID mortality rapidly decreased due to economic development and the expansion of health coverage in the 1980s, decelerated with increasing inequality, surged due to the 1997 economic crisis, and has gradually increased since the mid-2000s. The cohort effect showed an inverted U-shape. The increasing cohort effect due to the deterioration of living standards led to a decreasing trend after the independence of Korea. Notwithstanding the slowdown during the 1950–1953 Korean War, educational expansion, economic growth, fertility reduction, and the improvement of ID-related policies might have led to a continued decline among the cohorts born since the 1960s. Diverse socioeconomic events may have influenced ID mortality trends in Korea via period and cohort effects. Policies to reduce the growing burden of ID deaths should be further improved.
Green Gentrification and Health: A Scoping Review
Authors: Jelks Na’Taki Osborne , Jennings Viniece , Rigolon Alessandro
Published: January 2021

Urban greening initiatives are often linked to enhanced human health and wellbeing, but they can also be a driver of gentrification. To date, few studies have focused on how green gentrification shapes health. In this scoping review, we analyzed existing peer-reviewed research on how greening initiatives in gentrifying neighborhoods impact health, well-being, and health pathways (e.g., physical activity, affordable housing). Using a multi-step approach to scoping the literature (including searches in PubMed, JSTOR, and Google Scholar), we identified 15 empirical studies that met our inclusion criteria. We found studies focusing on green space use, physical activity, sense of community, safety, and self-reported health. Overall, longtime, marginalized residents are negatively impacted by green gentrification as they experience a lower sense of community, feel that they do not belong in green space, and, in many studies, use green space less often than newcomers. Overall, the research in this area is limited, and more studies on mental health and cardiovascular health markers could advance this literature. Based on the limited available evidence, we suggest that public health, urban planning, and parks professionals could collaborate to enhance the use of green space for marginalized residents and their feelings of inclusion in gentrifying areas.
Additive Manufacturing of Resected Oral and Oropharyngeal Tissue: A Pilot Study
Authors: Irace Alexandria L. , Koivuholma Anne , Huotilainen Eero , Hagström Jaana , Aro Katri , Salmi Mika , Markkola Antti , Sistonen Heli , Atula Timo , Mäkitie Antti A.
Published: January 2021

Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed using additive manufacturing techniques. Three patients diagnosed with oral/oropharyngeal cancer were included. All patients underwent preoperative magnetic resonance imaging followed by resection. In the operating room (OR), the resected tissue block was photographed using a smartphone. Digital photos were imported into Agisoft Photoscan to produce a digital 3D model of the resected tissue. Physical models were then printed using binder jetting techniques. The aforementioned process was applied in pilot cases including carcinomas of the tongue and larynx. The number of photographs taken for each case ranged from 63 to 195. The printing time for the physical models ranged from 2 to 9 h, costs ranging from 25 to 141 EUR (28 to 161 USD). Digital photography may be used to additively manufacture models of resected oral/oropharyngeal tumors in an easy, accessible and efficient fashion. The model may be used in interdisciplinary discussion regarding postoperative care to improve understanding and collaboration, but further investigation in prospective studies is required.
Urbanization’s Impacts on Ecosystem Health Dynamics in the Beijing-Tianjin-Hebei Region, China
Authors: Wu Fan , Wang Xiaoke , Ren Yufen
Published: January 2021

Accelerated urbanization disturbs ecosystems and influences ecosystem structures and functions. Ecosystem health (ESH) assessments in regions undergoing the rapid urbanization process assist us in understanding how ESH changes and how urbanization specifically affects ESH. We assessed the ESH of Beijing-Tianjin-Hebei (BTH) region, China, including the ecosystem service value (ESV). In this study, we selected nine indicators and applied multiple pieces of software, including ArcGIS10.4, Fragstats4.2 and Geoda1.14 to detect the impacts of urbanization on regional ESH in 1995, 2000, 2005, 2010 and 2015. The results show that ESH in the BTH region increased from 2000 to 2015, especially in the northern parts. The improvements were due to the implementation of key ecological restoration projects protecting and re-establishing the forest in the north. Furthermore, the spatial correlation results indicate that urbanization had a negative impact on ESH in the BTH region, of which the dominant factor was the population density in 1995. The dominant factor was the construction land proportion from 2005 to 2015. We suggest that ecological restoration projects should be continued in northern regions with strong and relatively strong ESH levels to maintain high-level ecosystem health. In addition, more attention should be paid to the ESH level improvement in peri-urban areas.
Screening of Emerging Pollutants (EPs) in Estuarine Water and Phytoremediation Capacity of Tripolium pannonicum under Controlled Conditions
Authors: Turcios Ariel E. , Hielscher Marie , Duarte Bernardo , Fonseca Vanessa F. , Caçador Isabel , Papenbrock Jutta
Published: January 2021

The increasing number of pharmaceuticals in the environment and their difficult biodegradation, can lead to bioaccumulation in different trophic compartments. Their bioaccumulation can have negative consequences, especially in the generation of bacterial resistance by antibiotics, but also in the impairment of plant and animal metabolism. The Tejo estuary in Portugal is the habitat for many plant and animal species, which are also prone to this type of contamination. Therefore, in the present study different classes of emerging pollutants (EPs) were surveyed in water samples in the Tejo estuary, including antibiotics, anticonvulsants, antidepressants, lipid-lowering drugs, anti-inflammatory drugs, beta-blockers and analgesics. According to the results, only four compounds were detected in water samples collected at the three selected salt marshes, including carbamazepine, fluoxetine hydrochloride, venlafaxine hydrochloride and acetaminophen. Having the detected substances as a basis, a subsequent study was performed aiming to investigate the uptake and biodegradation capacity of halophytes, using Tripolium pannonicum as a model plant cultivated under controlled conditions with different concentrations of the found EPs. This experimental approach showed that T. pannonicum was able to uptake and degrade xenobiotics. Moreover, the application of sulfamethazine, as a model antibiotic, showed also that this species can uptake and degrade this compound, although the degradation rate and process proved to be compound-specific. This was also confirmed using crude plant extracts spiked with the different EPs. Thus this species is a potential candidate for the remediation of marine water and sediments contaminated with environmentally-significant EPs.
Addendum: Sorgho, R., et al. Climate Change Policies in 16 West African Countries: A Systematic Review of Adaptation with a Focus on Agriculture, Food Security, and Nutrition. Int. J. Environ. Res. Public Health 2020, 17, 8897
Authors: Sorgho Raissa , Quiñonez Carlos A. Montenegro , Louis Valérie R. , Winkler Volker , Dambach Peter , Sauerborn Rainer , Horstick Olaf
Published: January 2021

The authors wish to make the following correction to this paper [...]
A Bibliometric Network Analysis of Coronavirus during the First Eight Months of COVID-19 in 2020
Authors: Furstenau Leonardo B. , Rabaioli Bruna , Sott Michele Kremer , Cossul Danielli , Bender Mariluza Sott , Farina Eduardo Moreno Júdice De Mattos , Filho Fabiano Novaes Barcellos , Severo Priscilla Paola , Dohan Michael S. , Bragazzi Nicola Luigi
Published: January 2021

The COVID-19 pandemic has affected all aspects of society. Researchers worldwide have been working to provide new solutions to and better understanding of this coronavirus. In this research, our goal was to perform a Bibliometric Network Analysis (BNA) to investigate the strategic themes, thematic evolution structure and trends of coronavirus during the first eight months of COVID-19 in the Web of Science (WoS) database in 2020. To do this, 14,802 articles were analyzed, with the support of the SciMAT software. This analysis highlights 24 themes, of which 11 of the more important ones were discussed in-depth. The thematic evolution structure shows how the themes are evolving over time, and the most developed and future trends of coronavirus with focus on COVID-19 were visually depicted. The results of the strategic diagram highlight ‘CHLOROQUINE’, ‘ANXIETY’, ‘PREGNANCY’ and ‘ACUTE-RESPIRATORY-SYNDROME’, among others, as the clusters with the highest number of associated citations. The thematic evolution. structure presented two thematic areas: “Damage prevention and containment of COVID-19” and “Comorbidities and diseases caused by COVID-19”, which provides new perspectives and futures trends of the field. These results will form the basis for future research and guide decision-making in coronavirus focused on COVID-19 research and treatments.
Pain Characteristics and Quality of Life in Older People at High Risk of Future Hospitalization
Authors: Johansson Maria M , Barbero Marco , Peolsson Anneli , Falla Deborah , Cescon Corrado , Folli Anna , Dong Huan-Ji
Published: January 2021

This study deals with how pain characteristics in conjunction with other factors affect quality of life (QoL) in a vulnerable primary care population. We recruited vulnerable older people (75+, n = 825) living in south-eastern Sweden. A postal questionnaire included pain aspects, QoL (EQ-5D-3L, RAND-36 physical functioning, attitudes toward own aging, and life satisfaction), functional status, social networks, and basic demographic information. Pain extent and localization was obtained by digitalization of pain drawings reported on standard body charts. Most respondents were experiencing pain longer than 3 months (88.8%). Pain frequency varied mostly between occasionally (33.8%) and every day (34.8%). A minority reported high pain intensity (13.6%). The lower back and lower legs were the most frequently reported pain locations (>25%). Multiple linear regression model revealed three characteristics of pain (intensity, frequency, and extent) remained inversely associated with the EQ-5D-3L index score (R2 = 0.57). Individually, each of these pain characteristics showed a negative impact on the other three dimensions of QoL (R2 = 0.23–0.59). Different features of pain had impact on different dimensions of QoL in this aging population. A global pain assessment is useful to facilitate individual treatment and rehabilitation strategies in primary care.
Development and Validation of a Questionnaire on Motivation for Cooperative Playful Learning Strategies
Authors: Manzano-León Ana , Camacho-Lazarraga Pablo , Guerrero-Puerta Miguel A. , Guerrero-Puerta Laura , Alias Antonio , Aguilar-Parra José M. , Trigueros Rubén
Published: January 2021

Playful learning strategies, such as educational gamification, game-based learning, and escape rooms are increasingly being incorporated into the university education system. In this study, it aims to develop and validate an instrument to analyze motivation regarding the use of playful learning strategies in university students. A total of 450 university students aged between 18 and 55 (Mean = 22.72; Standard Deviation = 5.01) were part of the sample, with whom playful strategies were implemented during the 2019/2020 school year. The results obtained in the confirmatory factor analysis indicate that the questionnaire on motivation for playful learning strategies has adequate psychometric properties to assess the motivation and perception of student learning in the implementation of ludic strategies in the classroom in the Spanish university context.
Cognition in Healthy Aging
Authors: Sánchez-Izquierdo Macarena , Fernández-Ballesteros Rocío
Published: January 2021

The study of cognitive change across a life span, both in pathological and healthy samples, has been heavily influenced by developments in cognitive psychology as a theoretical paradigm, neuropsychology and other bio-medical fields; this alongside the increase in new longitudinal and cohort designs, complemented in the last decades by the evaluation of experimental interventions. Here, a review of aging databases was conducted, looking for the most relevant studies carried out on cognitive functioning in healthy older adults. The aim was to review not only longitudinal, cross-sectional or cohort studies, but also by intervention program evaluations. The most important studies, searching for long-term patterns of stability and change of cognitive measures across a life span and in old age, have shown a great range of inter-individual variability in cognitive functioning changes attributed to age. Furthermore, intellectual functioning in healthy individuals seems to decline rather late in life, if ever, as shown in longitudinal studies where age-related decline of cognitive functioning occurs later in life than indicated by cross-sectional studies. The longitudinal evidence and experimental trials have shown the benefits of aerobic physical exercise and an intellectually engaged lifestyle, suggesting that bio-psycho-socioenvironmental factors concurrently with age predict or determine both positive or negative change or stability in cognition in later life.
Insulin’s Discovery: New Insights on Its Hundredth Birthday: From Insulin Action and Clearance to Sweet Networks
Authors: Leroux Melanie , Boutchueng-Djidjou Martial , Faure Robert
Published: January 2021

In 2021, the 100th anniversary of the isolation of insulin and the rescue of a child with type 1 diabetes from death will be marked. In this review, we highlight advances since the ingenious work of the four discoverers, Frederick Grant Banting, John James Rickard Macleod, James Bertram Collip and Charles Herbert Best. Macleoad closed his Nobel Lecture speech by raising the question of the mechanism of insulin action in the body. This challenge attracted many investigators, and the question remained unanswered until the third part of the 20th century. We summarize what has been learned, from the discovery of cell surface receptors, insulin action, and clearance, to network and precision medicine.
Unravelling the Complex Interplay of Transcription Factors Orchestrating Seed Oil Content in Brassica napus L.
Authors: Rajavel Abirami , Klees Selina , Schlüter Johanna-Sophie , Bertram Hendrik , Lu Kun , Schmitt Armin Otto , Gültas Mehmet
Published: January 2021

Transcription factors (TFs) and their complex interplay are essential for directing specific genetic programs, such as responses to environmental stresses, tissue development, or cell differentiation by regulating gene expression. Knowledge regarding TF–TF cooperations could be promising in gaining insight into the developmental switches between the cultivars of Brassica napus L., namely Zhongshuang11 (ZS11), a double-low accession with high-oil- content, and Zhongyou821 (ZY821), a double-high accession with low-oil-content. In this regard, we analysed a time series RNA-seq data set of seed tissue from both of the cultivars by mainly focusing on the monotonically expressed genes (MEGs). The consideration of the MEGs enables the capturing of multi-stage progression processes that are orchestrated by the cooperative TFs and, thus, facilitates the understanding of the molecular mechanisms determining seed oil content. Our findings show that TF families, such as NAC, MYB, DOF, GATA, and HD-ZIP are highly involved in the seed developmental process. Particularly, their preferential partner choices as well as changes in their gene expression profiles seem to be strongly associated with the differentiation of the oil content between the two cultivars. These findings are essential in enhancing our understanding of the genetic programs in both cultivars and developing novel hypotheses for further experimental studies.
Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A
Authors: Lin Xuguang , Watanabe Kenichi , Kuragano Masahiro , Tokuraku Kiyotaka
Published: January 2021

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.
Tryptophan Pathway Abnormalities in a Murine Model of Hereditary Glaucoma
Authors: Fiedorowicz Michal , Choragiewicz Tomasz , Turski Waldemar A. , Kocki Tomasz , Nowakowska Dominika , Wertejuk Kamila , Kamińska Agnieszka , Avitabile Teresio , Wełniak-Kaminska Marlena , Grieb Pawel , Zweifel Sandrine , Rejdak Robert , Toro Mario Damiano
Published: January 2021

Background: It has been shown that a possible pathogenetic mechanism of neurodegeneration in the mouse model of glaucoma (DBA/2J) may be an alteration of kynurenic acid (KYNA) in the retina. This study aimed to verify the hypothesis that alterations of tryptophan (TRP) metabolism in DBA/2J mice is not limited to the retina. Methods: Samples of the retinal tissue and serum were collected from DBA/2J mice (6 and 10 months old) and control C57Bl/6 mice of the same age. The concentration of TRP, KYNA, kynurenine (KYN), and 3-hydroxykynurenine (3OH-K) was measured by HPLC. The activity of indoleamine 2,3-dioxygenase (IDO) was also determined as a KYN/TRP ratio. Results: TRP, KYNA, L-KYN, and 3OH-K concentration were significantly lower in the retinas of DBA/2J mice than in C57Bl/6 mice. 3OH-K concentration was higher in older mice in both strains. Serum TRP, L-KYN, and KYNA concentrations were lower in DBA/2J than in age-matched controls. However, serum IDO activity did not differ significantly between compared groups and strains. Conclusions: Alterations of the TRP pathway seem not to be limited to the retina in the murine model of hereditary glaucoma.
Genetic and Environmental Factors Influence the Pleomorphy of LRRK2 Parkinsonism
Authors: Chittoor-Vinod Vinita G. , Nichols R. Jeremy , Schüle Birgitt
Published: January 2021

Missense mutations in the LRRK2 gene were first identified as a pathogenic cause of Parkinson’s disease (PD) in 2004. Soon thereafter, a founder mutation in LRRK2, p.G2019S (rs34637584), was described, and it is now estimated that there are approximately 100,000 people worldwide carrying this risk variant. While the clinical presentation of LRRK2 parkinsonism has been largely indistinguishable from sporadic PD, disease penetrance and age at onset can be quite variable. In addition, its neuropathological features span a wide range from nigrostriatal loss with Lewy body pathology, lack thereof, or atypical neuropathology, including a large proportion of cases with concomitant Alzheimer’s pathology, hailing LRRK2 parkinsonism as the “Rosetta stone” of parkinsonian disorders, which provides clues to an understanding of the different neuropathological trajectories. These differences may result from interactions between the LRRK2 mutant protein and other proteins or environmental factors that modify LRRK2 function and, thereby, influence pathobiology. This review explores how potential genetic and biochemical modifiers of LRRK2 function may contribute to the onset and clinical presentation of LRRK2 parkinsonism. We review which genetic modifiers of LRRK2 influence clinical symptoms, age at onset, and penetrance, what LRRK2 mutations are associated with pleomorphic LRRK2 neuropathology, and which environmental modifiers can augment LRRK2 mutant pathophysiology. Understanding how LRRK2 function is influenced and modulated by other interactors and environmental factors—either increasing toxicity or providing resilience—will inform targeted therapeutic development in the years to come. This will allow the development of disease-modifying therapies for PD- and LRRK2-related neurodegeneration.
Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies
Authors: Robinson Morgan , Lou Jennifer , Mehrazma Banafsheh , Rauk Arvi , Beazely Michael , Leonenko Zoya
Published: January 2021

Neurodegeneration in Alzheimer’s disease (AD) is defined by pathology featuring amyloid-β (Aβ) deposition in the brain. Aβ monomers themselves are generally considered to be nontoxic, but misfold into β-sheets and aggregate to form neurotoxic oligomers. One suggested strategy to treat AD is to prevent the formation of toxic oligomers. The SG inhibitors are a class of pseudopeptides designed and optimized using molecular dynamics (MD) simulations for affinity to Aβ and experimentally validated for their ability to inhibit amyloid-amyloid binding using single molecule force spectroscopy (SMFS). In this work, we provide a review of our previous MD and SMFS studies of these inhibitors and present new cell viability studies that demonstrate their neuroprotective effects against Aβ(1–42) oligomers using mouse hippocampal-derived HT22 cells. Two of the tested SG inhibitors, predicted to bind Aβ in anti-parallel orientation, demonstrated neuroprotection against Aβ(1–42). A third inhibitor, predicted to bind parallel to Aβ, was not neuroprotective. Myristoylation of SG inhibitors, intended to enhance delivery across the blood-brain barrier (BBB), resulted in cytotoxicity. This is the first use of HT22 cells for the study of peptide aggregation inhibitors. Overall, this work will inform the future development of peptide aggregation inhibitors against Aβ toxicity.
Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity
Authors: Meregalli Cristina , Monza Laura , Chiorazzi Alessia , Scali Carla , Guarnieri Chiara , Fumagalli Giulia , Alberti Paola , Pozzi Eleonora , Canta Annalisa , Ballarini Elisa , Rodriguez-Menendez Virginia , Oggioni Norberto , Cavaletti Guido , Marmiroli Paola
Published: January 2021

The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors’ quality of life. While recent studies have shown that neuroinflammation is involved in PTX-induced peripheral neurotoxicity (PIPN), the pathophysiology of this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated the effects of human intravenous immunoglobulin (IVIg) on a PIPN rat model. PTX-treated rats showed mechanical allodynia and neurophysiological alterations consistent with a severe sensory axonal polyneuropathy. In addition, morphological evaluation showed a reduction of intra-epidermal nerve fiber (IENF) density and evidenced axonopathy with macrophage infiltration, which was more prominent in the distal segment of caudal nerves. Three weeks after the last PTX injection, mechanical allodynia was still present in PTX-treated rats, while the full recovery in the group of animals co-treated with IVIg was observed. At the pathological level, this behavioral result was paralleled by prevention of the reduction in IENF density induced by PTX in IVIg co-treated rats. These results suggest that the immunomodulating effect of IVIg co-treatment can alleviate PIPN neurotoxic manifestations, probably through a partial reduction of neuroinflammation.
Sodium Salicylate Influences the Pseudomonas aeruginosa Biofilm Structure and Susceptibility Towards Silver
Authors: Gerner Erik , Almqvist Sofia , Thomsen Peter , Werthén Maria , Trobos Margarita
Published: January 2021

Hard-to-heal wounds are typically infected with biofilm-producing microorganisms, such as Pseudomonas aeruginosa, which strongly contribute to delayed healing. Due to the global challenge of antimicrobial resistance, alternative treatment strategies are needed. Here, we investigated whether inhibition of quorum sensing (QS) by sodium salicylate in different P. aeruginosa strains (QS-competent, QS-mutant, and chronic wound strains) influences biofilm formation and tolerance to silver. Biofilm formation was evaluated in simulated serum-containing wound fluid in the presence or absence of sodium salicylate (NaSa). Biofilms were established using a 3D collagen-based biofilm model, collagen coated glass, and the Calgary biofilm device. Furthermore, the susceptibility of 48-h-old biofilms formed by laboratory and clinical strains in the presence or absence of NaSa towards silver was evaluated by assessing cell viability. Biofilms formed in the presence of NaSa were more susceptible to silver and contained reduced levels of virulence factors associated with biofilm development than those formed in the absence of NaSa. Biofilm aggregates formed by the wild-type but not the QS mutant strain, were smaller and less heterogenous in size when grown in cultures with NaSa compared to control. These data suggest that NaSa, via a reduction of cell aggregation in biofilms, allows the antiseptic to become more readily available to cells.
Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches
Authors: Viglio Simona , Bak Elisabeth G. , Schouten Iris G. M. , Iadarola Paolo , Stolk Jan
Published: January 2021

As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 µM, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Because other therapies are still in the early phases of development, the only therapy currently available for AATD is AAT augmentation therapy. The controversy surrounding AAT augmentation therapy concerns its efficiency, as protection of lung function decline is not demonstrated, despite the treatment’s proven significant effect on lung density change in the long term. In this review article, novel biomarkers of NE and PR3 activity and their use to assess the efficacy of AAT augmentation therapy are discussed. Furthermore, a series of seven synthetic NE and PR3 inhibitors that can be used to evaluate the specificity of the novel biomarkers, and with potential as new drugs, are discussed.