bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifelong cognitive reserve, dementia, and mild cognitive impairment among older adults with limited education: a population-based cohort study
Authors: Li Yuanjing , Ren Yifei , Cong Lin , Hou Tingting , Song Lin , Wang Mingqi , Wang Xiang , Han Xiaojuan , Tang Shi , Zhang Qinghua , Dekhtyar Serhiy , Wang Yongxiang , Du Yifeng , Qiu Chengxuan 
Published: April 2022

Abstract
Background
Early-life educational attainment represents a major proxy for cognitive reserve (CR) that could benefit late-life cognitive function. We sought to investigate the associations of lifelong CR capacity with dementia and mild cognitive impairment (MCI) among people with limited education, while paying special attention to subtypes of dementia and MCI.
Methods
This population-based cohort study included 2127 participants (age ≥ 60 years; 59.4% women; 81.5% illiteracy or elementary school) who were free of dementia at baseline (August-December 2014) and undertook follow-up examinations in March-September 2018. Lifelong CR at baseline was estimated by integrating early-life education, adulthood occupation and marital status, and late-life physical activity, social activity, and social support using the structural equation models. Dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) were diagnosed following the international criteria. MCI and amnestic and non-amnestic MCI were defined following the Petersen’s criteria. Data were analyzed using Cox proportional-hazards models.
Results
During the total of 8330.63 person-years of follow-up, 101 were diagnosed with dementia, including 74 with AD and 26 with VaD. Medium and high (vs. low) tertiles of lifelong CR score were associated with multi-adjusted hazards ratio (95% confidence interval, CI) of 0.63 (0.40–1.00) and 0.27 (0.14–0.54) for dementia and 0.60 (0.35–1.02) and 0.18 (0.07–0.49) for AD. The association between higher CR and reduced AD risk was significant in young-old (60–74 years) but not in old-old people (≥ 75 years) (Pinteraction=0.011). Similarly, medium and high (vs. low) CR levels were associated with multi-adjusted hazard ratio (95% CI) of 0.81 (0.62–1.05) and 0.54 (0.40–0.73) for MCI and 0.73 (0.54–0.98) and 0.50 (0.36–0.70) for amnestic MCI. Lifelong CR was not significantly related to VaD or non-amnestic MCI. There was no statistical interaction of lifelong CR with sex and APOE genotype on incident dementia or MCI.
Conclusions
High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. The association of high CR with reduced AD risk existed only in young-old people. This study highlights the importance of lifelong CR in in maintaining late-life cognitive health even among people with limited education.
Contrasting continental patterns of adaptive population divergence in a holarctic fungus
Authors: Tremble Keaton , Hoffman Joseph , Dentinger Bryn 
Published: April 2022

Abstract
Understanding the population processes and genetic mechanisms that give rise to new species remains one of the most elusive goals of modern evolutionary biology. In the hyperdiverse and ecologically important Fungi, the process of speciation is virtually unknown, including for the more than 20,000 species of obligate ectomycorrhizal mutualists that play essential roles in ecosystem function. We investigated patterns of genome-wide differentiation in the ectomycorrhizal porcini mushroom Boletus edulis, a globally distributed species complex with broad ecological amplitude. By whole genome sequencing 160 individuals from across the Northern Hemisphere, we identified 792,923 SNPs and used these to elucidate the demographic and adaptive processes shaping global population differentiation. We show that B. edulis exhibits deeply contrasting patterns of genomic divergence between continents, with multiple lineages being present across North America, while a single lineage dominates Europe over a vast geographic scale. These geographical lineages are inferred to have diverged between 2.66 and 1.62 million years ago, corresponding to a period of climatic upheaval and the onset of glaciation during the Pliocene-Pleistocene boundary. High levels of genomic differentiation were observed among lineages despite evidence of substantial and ongoing introgression. Furthermore, genome scans, demographic inference and ecological niche models all suggest that genomic differentiation is maintained by environmental adaptation and not physical isolation. Our study uncovers striking differences on a truly global scale and emphasizes the importance of local adaptation and ecologically mediated divergence, rather than prezygotic barriers such as allopatry or genomic incompatibility in population differentiation in Fungi.
Travel Agent Students' English Reading Materials: Students' Perspective
Authors: Octaviana Sinta , Eryansyah Eryansyah , Inderawati Rita 
Published: April 2022

The study aims to study travel agent students' perception and needs toward English reading materials used in English learning at Vocational High School. Two sets of questionnaires were used to collect the data of the study. The first set of the questionnaire was used to find out students' perceptions, and the other one was used to analyze the needs of the students. The needs analysis was done based on four aspects of needs assessment: TSA, PSA, Deficiency Analysis, and Strategy Analysis. Afterwards, the obtained data were analyzed quantitatively. The results indicated that the students viewed English as an essential subject to learn. Furthermore, the students also perceived that integrating technology and Palembang culture into the English reading materials (textbook) was important in this 21st-century era. Besides, the students also believed that the current materials learned at school were not yet suitable for their needs, and they currently had difficulties learning English. In addition, the students hoped the reading materials contained the 21st-century skills and their local cultures related to their major. Based on the needs analysis results, further steps were necessary to provide the English reading materials integrated to Palembang local culture, which could facilitate students to improve their English proficiency in line with their department and the demands of the 21st century.
Nordic hydrological frontier in the 21st century
Authors: Marttila H. , Laudon H. , Tallaksen L. M. , Jaramillo F. , Alfredsen K. , Ronkanen A.-K. , Kronvang B. , Lotsari E. , Kämäri M. , Ala-Aho P. , Nousu J. , Silander J. , Koivusalo H. , Kløve B. 
Published: April 2022

AbstractThe 21st century has brought new challenges and opportunities and has also increased demands on the Nordic hydrological community. Our hydrological science focus and approaches need rethinking and adaptation to the changing requirements of society in response to climate change and human interventions, in search of more comprehensive and cross-disciplinary solutions. This commentary highlights new possibilities and suggests vital steps forward for the scientific discipline within Nordic hydrological research. By providing a common direction, we hope to increase awareness, accelerate progress in the hydrological community, and emphasize the importance of hydrological knowledge for serving other fields of science and society at large. We hope that our vision and the opportunities we identify will raise awareness of the scientific discipline and assist in the long-term development of the Nordic hydrological frontier in the 21st century.
LATIN AMERICAN COUNTRIES IN WORLD TRADE IN FOOD PRODUCTS
Authors: Yakovlev P. P. 
Published: April 2022

During the COVID-19 pandemic, there has been a marked increase in world prices for agricultural commodities, which has increased the value of international food trade. In other words, the coronavirus crisis, which has caused a decline in global trade, has hardly affected the interests of food producing and exporting countries. Many agricultural enterprises have become beneficiaries of the boom in international food markets. This was most clearly manifested in the markets for grains and oilseeds, as well as meat and meat products, where the positions of Latin American business structures are particularly strong. As the current trends demonstrate, the situation on the world food market favors the further growth of companies producing agricultural products in Latin America, primarily Brazil, which has firmly taken its place among the leading food exporting countries. These phenomena are of considerable interest to the Russian Federation, which, on the one hand, is a traditional importer of food products from Latin America, and on the other hand, itself is becoming an increasingly large producer and exporter of agricultural products, which leads to a reduction in purchases of certain types of food on the world market, including from Latin American countries.
Using the Knowledge Acquired During Studies in Shaping Attitudes Towards Sustainable Development
Authors: Jagodzińska Małgorzata , Strumińska-Doktór Anna 
Published: April 2022

Thanks to active education for sustainable development at universities, it is possible to prepare teachers ready to educate future generations of Polish learners on the one hand, and conscious economists, as well as political and social decision-makers able to introduce the principles of sustainable development in all spheres of human life, on the other. The aim of the research was to find out about the opinions of Polish students on how the knowledge acquired by them during their studies may shape their attitudes towards sustainable development. The research instruments used were a diagnostic survey method, with the help of the questionnaire technique. The research sample comprised 78 students representing the field of pedagogy studies, including 61.5% in the area of teacher studies (preschool and early school education) and 38.5% in the area of non-teaching studies (i.e., students without pedagogical qualifications, that is, educators who do not follow the core curriculum of general education[1]; such graduates perform educational and caring functions). A large percentage of respondents confirms the presence of the content related to sustainable development in their study programs, although its implementation is reported to occur to a small extent (marginally) only. The respondents who take into account the issues of sustainable development are involved to a greater extent in teacher education within the field of preschool and early school education. As part of the training activities for future teachers of kindergartens and primary school, grades 1-3, the teaching content has been integrated (with a module of socio-natural education being separated) that contains detailed learning outcomes evidently subordinated to the content of sustainable development. Although a clear difference in the use of knowledge in this area between students of teaching and non-teaching fields of study can be observed, it is still necessary to include the sustainable development related knowledge in the curricula of various study subjects, which will certainly affect the development of social capital, and thus education of people socially and environmentally responsible for their actions.

[1] Observed in the Polish context of higher education.
Role of Caffeine in the Age-related Neurodegenerative Diseases: A Review
Authors: Pohanka Miroslav 
Published: April 2022

Abstract:Caffeine, a simple purine alkaloid with the proper chemical name 1,3,7-trimethylpurine- 2,6-dione, is an abundant compound present in coffee, food and drugs. It interacts with various pathways of which antagonism of adenosine receptors is the most significant but the other physiological pathways can be influenced by caffeine as well. Interaction with glutamate and dopamine neurotransmission pathways, competition with other substrates on cytochrome P450, non-competitive inhibition of acetylcholinesterase, blocking of nicotinic acetylcholine receptor and competitive inhibition of cyclic nucleotide phosphodiesterase can be mentioned. Because of caffeine availability in foods, beverages and drugs, it has practical relevance even if the effect is weak. Intake of coffee containing edibles for a long period or even for a substantial part of life makes caffeine´s impact significant. Low acute and chronic toxicity of caffeine is another important specification. The discoveries from the last few years point to the fact that caffeine would interfere with the progression of some age-related neurodegenerative disorders like Alzheimer’s and Parkinson’s diseases and dementia with Lewy bodies. In this review article, the recent findings about caffeine´s impact on neurodegenerative diseases are presented and important facts about the caffeine effect, including the substantial discoveries, are described.
Probing the Synergistic Effect of Antibacterial Drug and Oleic Acid in
Lipid-based Gastroretentive Matrices by Melt Molding Method
Authors: Bhutta Zeeshan Ahmad , Arshad Amna , Khan Ikram Ullah , Ali Moazam , Arshad Fatima , Riaz Adeela , Ashar Ambreen 
Published: April 2022

Introduction:
Clarithromycin (antibiotic), due to its narrow absorption window in the gastrointestinal
tract, was taken as a model drug.

Materials & Methods:
Focusing on the efficient drug delivery system, floating tablets that remain
buoyant over gastric fluid for 24 hrs were produced by adopting the melt mold method using beeswax,
gelucire, and oleic acid. To modulate the release pattern, a different concentration of 48/16 of beeswax
and gelucire was used.

Results:
To evaluate and characterize the final product, several tests, including the percentage recovery,
in-vitro release studies, clarithromycin loading, scanning electron microscopy, differential scanning
calorimeter, X-ray powder diffractometry, fourier transform infrared spectroscopy, weight variation,
hardness, and friability, were carried out. Regarding the results, the encapsulation efficiency of the
floating tablets was 39.5% to 59%, having weight variation with and without gelucire as 48/16
0.09525±0.0032g, and 0.09527±0.00286g to 0.0957±0.00321g, respectively. Clarithromycin release
was controlled by using hydrophobic beeswax and hydrophilic gelucire 48/16. X-ray powder diffractometry,
differential scanning calorimeter, and fourier transform infrared spectroscopy confirmed the
absence of drug-polymer interaction, and exhibited amorphous and crystalline form of the drug after
encapsulation. Drug release kinetics was determined by applying different models, such as zero-order,
first-order model, Higuchi, and Korsemeyer-Pappas model. All formulations followed the Korsmeyer-
Peppas model at 1.2 pH.

Conclusion:
Gastroretentive drug delivery systems were produced by using melt molding technique. In
vitro dissolution represents the sustained release of the drug from the formulation.
Emerging Trends and Potential Prospects in Vaginal Drug Delivery
Authors: Mahant Shikha , Sharma Abhishek Kumar , Gandhi Himanshu , Wadhwa Ridhima , Dua Kamal , Kapoor Deepak N. 
Published: April 2022

Abstract:
The vagina is an essential part of the female reproductive system and offers many potential
benefits over conventional drug delivery, including a large surface area for drug absorption, relatively
low enzymatic activity, avoiding first-pass effects, and ease of administration. The vaginal
mucosal cavity is an effective route for administering therapeutic agents that are intended both for
local and systemic administration. The present review provides a comprehensive overview of recent
trends and developments in vaginal drug delivery. Marketed formulations and products under clinical
study are also reviewed. Various novel vaginal delivery systems have been studied in recent
years as effective tools for delivering a range of therapeutic agents to the vagina. These systems offer
numerous benefits, including sustained delivery, improved bioavailability, effective permeation,
and higher efficacy. The recent focus of the scientific community is on the development of safe and
efficient drug delivery systems, such as nanoparticles, microparticles, vesicular systems, vaginal
rings, microneedles, etc., for vaginal application. Various factors, such as the physicochemical properties
of the drugs, the volume and composition of the vaginal fluid, the pH of the vaginal fluid, the
thickness of the vaginal epithelium, and the influence of sexual intercourse may influence the release
of drugs from the delivery system and subsequent absorption from the vaginal route. To date,
only a limited number of in vivo studies on novel vaginal DDS have been reported. Additionally,
drug release kinetics under varying vaginal environments is also not well understood. More research
is needed to ensure the suitability, biocompatibility, and therapeutic effectiveness of novel DDS for
vaginal delivery. Although numerous strategies and interventions have been developed, clinical
translation of these systems remains a challenge. The toxicity of the carrier system is also an important
consideration for future clinical applications.
Fighting Carcinogenesis with Plant Metabolites by Weakening Proliferative
Signaling and Disabling Replicative Immortality Networks of Rapidly
Dividing and Invading Cancerous Cells
Authors: El-Zahaby Sally A. , Wani Atif Khurshid , Akhtar Nahid , Sharma Arun 
Published: April 2022

Background:
Cancer, an uncontrolled multistage disease causing swift division of cells, is a
leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors,
resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic
action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The
innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling,
enabling replicative immortality through telomere dysfunction.

Area Covered:
The conventional genotoxic drugs have several off-target and collateral side effects
associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling
pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis,
and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from
plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific,
making them biologically significant. This has opened a gateway for the exploration of more
novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them
more effective than the existing cytotoxic regimens.

Expert Opinion:
In this context, the current review presented recent data on cancer cases around the
globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of
cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action
of plant-derived compounds, besides explaining the need for improving drug delivery systems.
Co-Treatment with the Herbal Medicine SIP3 and Donepezil Improves
Memory and Depression in the Mouse Model of Alzheimer’s Disease
Authors: Liu Quan Feng , Choi Hoon , Son Taekwon , Kim Young-Mi , Kanmani Suganya , Chin Young-Won , Kim Seung-Nam , Kim Kwang Ki , Kim Kyu-Won , Koo Byung-Soo 
Published: April 2022

Background:
Alzheimer’s disease (AD) is a lethal, progressive neurodegenerative disorder
that has been linked to a deficiency of the neurotransmitter acetylcholine. Currently, many acetylcholinesterase
inhibitors, such as donepezil, are widely used for the treatment of AD. On the other hand, the
efficacy of long-term donepezil use is limited. SIP3, a mixture of three herbal extracts from Santalum
album, Illicium verum, and Polygala tenuifolia, is a new formula derived from traditional Korean herbal
medicine.

Objective:
We assessed the synergistic effect of SIP3 and donepezil co-treatment on symptoms of AD
using APP/PS1 transgenic mice.

Methods:
In this study, a Drosophila AD model and SH-SY5Y clles were used to assess the toxicity of
SIP3, and APPswe/PS1dE9 (APP/PS1) transgenic mice were used to evaluate the cognitive-behavioral
and depression-like behavior effect of SIP3 and donepezil co-treatment on symptoms of AD. The cerebral
cortex or hippocampus transcriptomes were analyzed by RNA sequencing and miRNA to investigate
the molecular and cellular mechanisms underlying the positive effects of SIP3 on AD.

Results:
In the passive avoidance test (PAT) and Morris water maze (MWM) test, the combination of
SIP3 and donepezil improved the learning capabilities and memory of APP/PS1 mice in the mid-stage
of AD compared to the group treated with donepezil only. In addition, co-administration of SIP3 and
donepezil effectively reduced the depression-like behavior in the forced swimming and tail suspension
tests. Furthermore, RNA sequencing of the cerebral cortex transcriptome and miRNA of the hippocampus
showed that the gene expression profiles after a low dose SIP3 co-treatment were more similar to
those of the normal phenotype mice than those obtained after the donepezil treatment alone. The Gene
Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, showed that
differentially expressed genes were involved in the locomotor behavior and neuroactive ligand-receptor
interactions. These results suggest that a co-treatment of low dose SIP3 and donepezil improves impaired
learning, memory, and depression in the mid-stage of AD in mice.

Conclusion:
Co-treatment of low dose SIP3 and donepezil improves impaired learning, memory, and
depression in the mid-stage of AD in mice.
Catalyst-free, One-pot Synthesis of 2-Aryl Benzimidazoles from Orthophenylenediamine
and Aryl Aldehyde in Acetonitrile
Authors: Khatik Gopal L. 
Published: April 2022

Aim:
The study aims to optimize and synthesize benzimidazole derivatives.

Background:
Benzimidazoles are essential intermediates and scaffolds for biological activity and drug
substances. The reported syntheses of benzimidazoles suffer from disadvantages like longer reaction
time using a catalyst, which makes the method costly, and the use of strong corrosive acids and toxic
reagents that increase environmental hazards.

Objectives:
One-pot synthesis of 2-aryl benzimidazole from ortho-phenylenediamine and aryl aldehyde.

Method:
Herein disclosed a catalyst-free, one-pot synthesis of 2-aryl benzimidazole.

Results:
Different 2-aryl benzimidazoles were synthesized in good yields via the condensation reaction
of aryl aldehyde and ortho-phenylenediamine in acetonitrile as a solvent at room temperature. The
method is very simple and convenient, with good yields. The formation of the desired product is affected
by the substituent of aryl aldehydes. Electron donating substituents are shown to have a higher
time in the completion of a reaction than electron-withdrawing substituents.

Conclusions:
One-pot synthesis of benzimidazole was found to be simpler and economical.