bluuebunny/crossref_metadata_2025 huggingface dataset:
Balkan countries on the way to the European Union:
experience for Ukraine
Authors: Kyfyak Viktoriia
Published: June 2022

Summary. Fluctuations that change the business environment, such
as pandemics and hostilities, necessitate a change in the paradigm of
business management, in which risk management and digitalization are
the basis of competitive business models, which makes the topic relevant
in today’s complex business realities.
The aim of the article is to substantiate the institutional support
of risk management and digital tools as a necessary component of business models in modern conditions.
Research methodology. The article uses methods of systematic approach and structuring as a basis for identifying the main problems
and trends in the development of risk management mechanism in the
context of digitalization. And also used such general scientific methods
as analysis, synthesis and dialectics.
Novelty. The article identifies the dynamics of changes in risk management paradigms in the enterprise management system.
It is substantiated that multilevel and multifaceted nature of risk
requires study of the structure of risks and the mechanism of their
impact on the enterprise through the prism of the institutional environment, which determines the features and specification of the transformation of the factor into a source of risk in a given period and
territory.
It is proposed to apply the coefficient of digitalization of business
processes, which will determine the degree of dependence of the business process on digital threats.
It is proposed to determine the institutional support for risk discrimination, through the results of institutions aimed at monitoring
and identifying external business risks and those based on operational
data on fluctuations in the economic system.
Conclusions. The institutions of risk management in the conditions
of digitalization are defined and characterized and the risks that
threaten in these conditions are identified. Key global trends in corporate security have been studied. The digital tools such as cognitive
computing, ERP and MES systems and SAS-style software for risk
management and for building an effective business model in the face
of new social challenges are described.
Efektivitas Zoom Cloud Meeting dalam Pendidikan Jarak Jauh Di Masa Pandemi Covid-19
Authors: Raihan Ramzi  , Cynthia Johan Riche
Published: June 2022

Pandemi COVID-19 membawa perubahan dalam bidang pendidikan di Indonesia. Pembelajaran yang semula menggunakan modus konvensional, saat ini beralih menggunakan modus pembelajaran jarak jauh (PJJ), salah satunya dengan memanfaatkan video conference Zoom Cloud Meeting. Artikel ini bertujuan menggambarkan efektifitas Zoom Cloud Meeting dalam PJJ. Menggunakan metode studi pustaka, studi ini menggambarkan bagaimana fitur-fitur yang tersedia pada aplikasi Zoom Cloud Meeting mendukung untuk melakukan kegaiatan pembelajaran jarak jauh. Selain itu, Zoom Cloud Meeting cenderung efektif untuk pembelajaran non-praktik dan bagi peserta didik dengan gaya belajar audio dan visual.
The Effect Of Sustainable Professional Development On The Competence And Performance Of Elementary School Teachers In Learning Innovation
Authors: Nurmalina Nurmalina , Suhartono Suhartono
Published: June 2022

The research aims to describe the effect of Continuing Professional Development (PKB) on the competence and performance of elementary school teachers in learning innovation, and analyze how much influence PKB has on the competence and performance of elementary school teachers in carrying out learning innovations. Quantitative research method with simple random sampling technique. The population is 116 people and the sample used is 90 respondents. The resulting instruments include: PKB planning, self-development, scientific publications and innovative works with indicators following and implementing training, workshops, seminars, making innovative works and scientific publications in teacher performance. While learning innovation is measured through learning programs, classroom management, mastery of teaching materials, use of methods, media and evaluation of learning. The application of reflective actions and the results of Classroom Action Research reports on a regular basis become a benchmark for more professional teacher performance. Statistical data shows that: 1) there is a positive and significant effect of the PKB variable on teacher competence by 9.28%, 2) there is a positive and significant effect of the PKB variable on teacher performance by 4.84% and 3) there is a positive and significant influence on teacher performance. Simultaneous PKB variable on teacher competence and performance is 14.12%. Continuing Professional Development has a significant influence on teacher competence and performance which can be designed, tested and measured by the relevant agencies and has a broad impact on the innovative culture of teacher learning during the pandemic.
Pendidikan Karakter Siswa Sekolah Dasar Pada Masa Pandemi Covid-19
Authors: Fatimah Siti , Sudi Pratikno Ahmad
Published: June 2022

Pandemi Covid-19 memiliki banyak dampak terhadap kehidupan bermasyarakat. Salah satu perubahan yang dirasakan adalah dalam bidang pendidikan di mana pembelajaran di sekolah diputuskan untuk dilaksanakan secara online. Pada masa pandemi Covid-19, pendidikan karakter tidak boleh diabaikan begitu saja, terutama di jenjang sekolah dasar. Pada jenjang ini, pendidikan karakter sangat dibutuhkan untuk perkembangan para siswa. Artikel ini bertujuan untuk mengetahui bagaimana pelaksanaan pendidikan karakter dalam pembelajaran selama masa pandemi Covid-19 di sekolah dasar. Metode yang digunakan dalam studi ini adalah kajian pustaka. Hasil studi menunjukkan bahwa pendidikan karakter dibutuhkan oleh siswa sekolah dasar meskipun pembelajaran harus dilaksanakan di rumah. Pendidikan karakter melalui pembelajaran jarak jauh tidak boleh diabaikan dan harus menyesuaikan dengan kondisi siswa serta situasi Covid-19. Kesimpulan dari studi ini adalah guru harus mengintegrasikan nilai-nilai karakter dalam setiap muatan pembelajaran, seperti nilai religius, tanggungjawab, toleransi, dan kerja keras.
Measuring Level of Students’ Independent Learning In Distance Learning
Authors: Rahayu Annisa Nuraeni , Mujdalipah Siti , R Dwi Lestari
Published: June 2022

This study aims to determine the level of students’ independent learning based on indicators of independent learning in terms of the process and management of students when they were studying. When students learn independently, it plays an important role in learning success and helping students obtained optimal learning outcomes. This research was used analytic descriptive research methods and survey techniques, used four indicators of independent learning in terms of the process and management of students when they were studying. The results showed that most of the students had independent learning in high to very high categories on the indicators of having initiative and motivation to learning, able to diagnose learning needs, able to determine learning targets and learning goals, and able to monitor, organize, and control learning. The results showed that almost all students had a level of independent learning in the high to the very high category on those three indicators.
Rank–Polyserial Correlation: A Quest for a “Missing” Coefficient of Correlation
Authors: Metsämuuronen Jari
Published: June 2022

In the typology of coefficients of correlation, we seem to miss such estimators of correlation as rank–polyserial (RRPS) and rank–polychoric (RRPC) coefficients of correlation. This article discusses a set of options as RRP, including both RRPS and RRPC. A new coefficient JTgX based on Jonckheere–Terpstra test statistic is derived, and it is shown to carry the essence of RRP. Such traditional estimators of correlation as Goodman–Kruskal gamma (G) and Somers delta (D) and dimension-corrected gamma (G2) and delta (D2) are shown to have a strict connection to JTgX, and, hence, they also fulfil the criteria for being relevant options to be taken as RRP. These estimators with a directional nature suit ordinal-scaled variables as well as an ordinal- vs. interval-scaled variable. The behaviour of the estimators of RRP is studied within the measurement modelling settings by using the point-polyserial, coefficient eta, polyserial correlation, and polychoric correlation coefficients as benchmarks. The statistical properties, differences, and limitations of the coefficients are discussed.
Security Monitoring Strategy of Distribution Community Operation Site Based on Intelligent Image Processing Method
Authors: Sun Zhiqing , Xuan Yi , Fan Libo , Han Rongjie , Tu Yongwei , Huang Jiabin , Xiang Xinyu , Wang Yi , Fang Xiang
Published: June 2022

With the continuous development of energy infrastructure, a large number of distributed new energy, distributed energy storage, and various power electronic equipment are connected to distribution communities. The access to a large amount of equipment not only increases the workload of power operators, but also leads to a complex field operation environment, which will threaten the security of field operators. Traditional monitoring strategy for distribution community operation site relies on manual operation, which is tedious, labor-intensive, and error-prone. To solve this problem, this paper proposes a security monitoring strategy for distribution community operation sites based on an intelligent image processing method. Firstly, a power image enhancement method based on multi-filtering algorithm is proposed. The filter operators are used to smooth and denoise the image, enhance the edge and detail information, and expand the security monitoring data set of operation sites by merging the filtered images. Secondly, an object detection method for personnel and security protection tools based on the improved Faster R-CNN algorithm is proposed, and a pyramid structure is constructed to improve the detection and localization accuracy of small objects such as safety helmets and safety belts. To simplify the object detection task and the complexity of the labeling system, it is disassembled into four single tasks: operators, non-operators, safety helmets, and safety belts. Finally, the detection frame labels are fused by calculating the overlap of the object detection boxes to describe the security of the operator. Experiments show that the method proposed in this paper can effectively locate the object and accurately describe the security of the operator.
Psychological Welfare Loss of Land-Expropriated Farmers in China
Authors: Xiao Lifu , Qu Lu , Wang Lei , Hu Zhiling , Xiao Feilong , Lin Qiaowen
Published: June 2022

Mandatory land expropriation, resettlement and welfare loss of landless peasants have received increasing research attention. However, in most previous analyses, the loss of psychological welfare of landless farmers is often neglected, which may lead to biased land requisition compensation and resettlement programs and incomplete policy recommendations. This study attempts to use a three-dimensional framework of place attachment to analyze the causes of psychological welfare loss. China’s land expropriation and centralized resettlement cut off the material and emotional ties between farmers and land. Farmers’ dependence on land, or their dependence on land-dependent farming lifestyle, has been neglected in the process of land acquisition and resettlement, resulting in the loss of farmers’ psychological welfare. Based on a comparative analysis of the existing methods, this paper chooses the contingent valuation method (CVM) to measure the loss of psychological welfare of landless peasants via monetization. The feasibility of the model has been tested at a small scale in nine cities. The results show that 1) farmers have strong place attachment on agricultural land, although centralized land expropriation and resettlement have neglected this dependence and caused psychological welfare losses to landless peasants; and 2) the loss of psychological welfare of landless peasants can be measured by the CVM and presented in monetary units. The monetization measurement method in this paper still has some shortcomings and its feasibility requires more empirical tests. However, as a rare monetization measurement study, this paper can direct academic and policy attention towards this psychological welfare loss.
Uniparental Genetic Analyses Reveal Multi-Ethnic Background of Dunhuang Foyemiaowan Population (220–907 CE) With Typical Han Chinese Archaological Culture
Authors: Xiong Jianxue , Tao Yichen , Ben Minxi , Yang Yishi , Du Panxin , Allen Edward , Wang Hui , Xu Yiran , Yu Yao , Meng Hailiang , Bao Haoquan , Zhou Boyan , Chen Guoke , Li Hui , Wen Shaoqing
Published: June 2022

The relationship between archeological culture and ethnicity is invariably complex. This is especially the case for periods of national division and rapid inter-ethnic exchange, such as China’s Sixteen Kingdoms (304–439 CE) and Northern and Southern Dynasties (420–589 CE). Going by tomb shape and grave goods, the Foyemiaowan cemetery at Dunhuang exhibits a typical third–tenth century Han style. Despite this, the ethnic makeup of the Foyemiaowan population has remained unclear. We therefore analyzed 485 Y-chromosomal SNPs and entire mitochondrial genomes of 34 Foyemiaowan samples. Our study yielded the following discoveries: (1) principal component analysis revealed that the Foyemiaowan population was closely clustered with Tibeto-Burman populations on the paternal side and close to Mongolic-speaking populations on the maternal side; (2) lineage comparisons at the individual level showed that the Foyemiaowan population consisted of primarily Tibeto-Burman and Han Chinese related lineages (Oα-M117, 25%;Oβ-F46, 18.75%), partially Altaic speaking North Eurasian lineages (N-F1206, 18.75%) and a slight admixture of southern East Asian lineages (O1b1a2-Page59, 6.25%; O1b1a1-PK4, 3.13%). Similarly, the maternal gene pool of Foyemiaowan contained northern East Asian (A, 4.17%; CZ, 16.67%; D, 20.83%; G, 4.17%; M9, 4.17%), southern East Asian (B, 12.51%; F, 20.83%) and western Eurasian (H, 4.17%; J, 4.17%) related lineages; (3) we discovered a relatively high genetic diversity among the Foyemiaowan population (0.891) in our ancient reference populations, indicating a complex history of population admixture. Archeological findings, stable isotope analysis and historical documents further corroborated our results. Although in this period China’s central government had relinquished control of the Hexi Corridor and regional non-Han regimes became the dominant regional power, Foyemiaowan’s inhabitants remained strongly influenced by Han culture.
Meiotic Silencing in Dothideomycetous Bipolaris maydis
Authors: Tsuji Kenya , Kitade Yuki , Yoshimi Akira , Tanaka Chihiro
Published: June 2022

The filamentous ascomycete Bipolaris maydis is a plant pathogen that causes corn leaf blight and has been used in cytological studies of sexual reproduction. In this fungus, when null mutants of each septin are crossed with the wild-type strain, all ascospores derived from the same asci show abnormal morphology. The phenomenon was remarkably similar to the event known as “ascus dominance” in Neurospora crassa, which is known to be caused by MSUD (meiotic silencing by unpaired DNA). However, it is not clear whether B. maydis possesses functional MSUD. The object of this study is to elucidate whether this fungus carries a functional MSUD system that causes ascus dominance in the crosses of septin mutants and the wild-type strain. The results of homozygous and heterozygous crossing tests with mutants, having the insertional CDC10-septin gene sequence into the genome, suggested that the ascus dominance in B. maydis is triggered by the unpaired DNA as in N. crassa. To investigate whether MSUD is caused by the same mechanism as in N. crassa, an RNA-dependent RNA polymerase, one of the essential factors in MSUD, was identified and disrupted (Δrdr1) in B. maydis. When the Δrdr1 strain was crossed with each mutant of the septins, ascus dominance did not occur in all crosses. These results suggest that this ascus dominance is caused by RNA silencing triggered by an unpaired gene, as in N. crassa, and septin genes were affected by this silencing. To date, although MSUD has been found only in Fusarium graminearum and N. crassa, which are classified as Sordariomycetes, this study showed that MSUD is also functional in B. maydis, which is classified as a Dothideomycete. These results showed the possibility that this posttranscriptional regulation is extensively conserved among filamentous ascomycetes.
Risk Stratification and Validation of Eleven Autophagy-Related lncRNAs for Esophageal Squamous Cell Carcinoma
Authors: Zhao Xu , Wang Yulun , Meng Fanbiao , Liu Zhuang , Xu Bo
Published: June 2022

Esophageal squamous cell carcinoma (ESCC), the most prevalent subtype of esophageal cancer, ranks sixth in cancer-related mortality, making it one of the deadliest cancers worldwide. The identification of potential risk factors for ESCC might help in implementing precision therapies. Autophagy-related lncRNAs are a group of non-coding RNAs that perform critical functions in the tumor immune microenvironment and therapeutic response. Therefore, we aimed to establish a risk model composed of autophagy-related lncRNAs that can serve as a potential biomarker for ESCC risk stratification. Using the RNA expression profile from 179 patients in the GSE53622 and GSE53624 datasets, we found 11 lncRNAs (AC004690.2, AC092159.3, AC093627.4, AL078604.2, BDNF-AS, HAND2-AS1, LINC00410, LINC00588, PSMD6-AS2, ZEB1-AS1, and LINC02586) that were co-expressed with autophagy genes and were independent prognostic factors in multivariate Cox regression analysis. The risk model was constructed using these autophagy-related lncRNAs, and the area under the receiver operating characteristic curve (AUC) of the risk model was 0.728. To confirm that the model is reliable, the data of 174 patients from The Cancer Genome Atlas (TCGA) esophageal cancer dataset were analyzed as the testing set. A nomogram for ESCC prognosis was developed using the risk model and clinic-pathological characteristics. Immune function annotation and tumor mutational burden of the two risk groups were analyzed and the high-risk group displayed higher sensitivity in chemotherapy and immunotherapy. Expression of differentially expressed lncRNAs were further validated in human normal esophageal cells and esophageal cancer cells. The constructed lncRNA risk model provides a useful tool for stratifying risk and predicting the prognosis of patients with ESCC, and might provide novel targets for ESCC treatment.
A Review of Methodologies for the Detection, Quantitation, and Localization of Free Cysteine in Recombinant Proteins: A Focus on Therapeutic Monoclonal Antibodies
Authors: Metcalfe Clive
Published: June 2022

Free-cysteine residues in recombinant biotherapeutics such as monoclonal antibodies can arise from incorrect cellular processing of disulfide bonds during synthesis or by reduction of disulfide bonds during the harvest and purification stage of manufacture. Free cysteines can affect potency, induce aggregation, and decrease the stability of therapeutic proteins, and the levels and positions of free cysteines in proteins are closely monitored by both manufacturers and regulators to ensure safety and efficacy. This review summarizes the latest methodologies for the detection and quantification of free cysteines.
Human Claudin-7 cis-Interactions Are Not Crucial for Membrane-Membrane (Trans-) Interactions
Authors: Ahlswede Lena , Siebenaller Carmen , Junglas Benedikt , Hellmann Nadja , Schneider Dirk
Published: June 2022

Human Claudin-7 (Cldn7) is a member of the Claudin (Cldn) superfamily. In vivo, these proteins form tight junctions, which establish constricted connections between cells. Cldns oligomerize within the membrane plane (= cis-interaction), and also interact with Cldns from adjacent cells (= trans-interaction). Interactions of Cldns are typically studied in vivo and structural analyses of isolated Cldns are limited. Here, we describe heterologous expression in E. coli and purification of human Cldn7, enabling in vitro analyses of the isolated protein using detergent and model membrane systems. Cldn7 exists as a monomer, hexamer, and various higher oligomers in micelles. While only limited unfolding of the protein was observed in the presence of the anionic detergent sodium dodecyl sulfate, decreased ionic strength did affect Cldn7 cis-interactions. Furthermore, we identified two amino acids which mediate electrostatic cis-interactions and analyzed the impact of disturbed cis-interaction on trans-contacts via atomic force microscopy and monitoring Förster resonance energy transfer between fluorescently labeled Cldn7-containing proteoliposomes. Our results indicate that Cldn7 cis-oligomerization might not be a prerequisite for establishing trans-contacts.
Affective Enhancement of Episodic Memory Is Associated With Widespread Patterns of Intrinsic Functional Connectivity in the Brain Across the Adult Lifespan
Authors: Katsumi Yuta , Moore Matthew
Published: June 2022

Subjectively arousing experiences tend to be better remembered than neutral ones. While numerous task-related neuroimaging studies have revealed the neural mechanisms associated with this phenomenon, it remains unclear how variability in the extent to which individuals show superior memory for subjectively arousing stimuli is associated with theintrinsicfunctional organization of their brains. Here, we addressed this issue using functional magnetic resonance imaging data collected at rest from a sample drawn from the Cambridge Centre for Ageing and Neuroscience cohort (N= 269, 18–86 years). Specifically, we performed multi-voxel pattern analysis of intrinsic functional connectivity, an unbiased, data-driven approach to examine whole-brain voxel-wise connectivity patterns. This technique allowed us to reveal the most important features from the high-dimensional, whole-brain connectivity structure withouta priorihypotheses about the topography and direction of functional connectivity differences. Behaviorally, both item and associative memory accuracy were enhanced for trials with affectively arousing (positive or negative) stimuli than those with neutral ones. Whole-brain multi-voxel pattern analysis of functional connectivity revealed that the affective enhancement of memory was associated with intrinsic connectivity patterns of spatially distributed brain regions belonging to several functional networks in the cerebral cortex.Post hocseed-based brain-behavior regression analysis and principal component analysis of the resulting correlation maps showed that these connectivity patterns were in turn primarily characterized by the involvement of heteromodal association and paralimbic (dorsal attention, salience, and default mode) networks of the cerebral cortex as well as select subcortical structures (striatum, thalamus, and cerebellum). Collectively, these findings suggest that the affective enhancement of episodic memory may be characterized as a whole-brain phenomenon, possibly supported by intrinsic functional interactions across several networks and structures in the brain.
Adaptive Bilateral Texture Filter for Image Smoothing
Authors: Xu Huiqin , Zhang Zhongrong , Gao Yin , Liu Haizhong , Xie Feng , Li Jun
Published: June 2022

The biggest challenge of texture filtering is to smooth the strong gradient textures while maintaining the weak structures, which is difficult to achieve with current methods. Based on this, we propose a scale-adaptive texture filtering algorithm in this paper. First, the four-directional detection with gradient information is proposed for structure measurement. Second, the spatial kernel scale for each pixel is obtained based on the structure information; the larger spatial kernel is for pixels in textural regions to enhance the smoothness, while the smaller spatial kernel is for pixels on structures to maintain the edges. Finally, we adopt the Fourier approximation of range kernel, which reduces computational complexity without compromising the filtering visual quality. By subjective and objective analysis, our method outperforms the previous methods in eliminating the textures while preserving main structures and also has advantages in structure similarity and visual perception quality.
Establishment and Validation of a Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Lower-Grade Glioma
Authors: Huang Qian-Rong , Li Jian-Wen , Yan Ping , Jiang Qian , Guo Fang-Zhou , Zhao Yin-Nong , Mo Li-Gen
Published: June 2022

Background

The prognosis of lower-grade glioma (LGG) is highly variable, and more accurate predictors are still needed. The aim of our study was to explore the prognostic value of ferroptosis-related long non-coding RNAs (lncRNAs) in LGG and to develop a novel risk signature for predicting survival with LGG.

Methods

We first integrated multiple datasets to screen for prognostic ferroptosis-related lncRNAs in LGG. A least absolute shrinkage and selection operator (LASSO) analysis was then utilized to develop a risk signature for prognostic prediction. Based on the results of multivariate Cox analysis, a prognostic nomogram model for LGG was constructed. Finally, functional enrichment analysis, single-sample gene set enrichment analysis (ssGSEA), immunity, and m6A correlation analyses were conducted to explore the possible mechanisms by which these ferroptosis-related lncRNAs affect survival with LGG.

Results

A total of 11 ferroptosis-related lncRNAs related to the prognosis of LGG were identified. Based on prognostic lncRNAs, a risk signature consisting of 8 lncRNAs was constructed and demonstrated good predictive performance in both the training and validation cohorts. Correlation analysis suggested that the risk signature was closely linked to clinical features. The nomogram model we constructed by combining the risk signature and clinical parameters proved to be more accurate in predicting the prognosis of LGG. In addition, there were differences in the levels of immune cell infiltration, immune-related functions, immune checkpoints, and m6A-related gene expression between the high- and low-risk groups.

Conclusion

In summary, our ferroptosis-related lncRNA signature exhibits good performance in predicting the prognosis of LGG. This study may provide useful insight into the treatment of LGG.
Detection of Transcranial Alternating Current Stimulation Aftereffects Is Improved by Considering the Individual Electric Field Strength and Self-Rated Sleepiness
Authors: Steinmann Iris , Williams Kathleen A. , Wilke Melanie , Antal Andrea
Published: June 2022

Non-invasive electrical stimulation methods, such as transcranial alternating current stimulation (tACS), are increasingly used in human neuroscience research and offer potential new avenues to treat neurological and psychiatric disorders. However, their often variable effects have also raised concerns in the scientific and clinical communities. This study aims to investigate the influence of subject-specific factors on the alpha tACS-induced aftereffect on the alpha amplitude (measured with electroencephalography, EEG) as well as on the connectivity strength between nodes of the default mode network (DMN) [measured with functional magnetic resonance imaging (fMRI)]. As subject-specific factors we considered the individual electrical field (EFIELD) strength at target regions in the brain, the frequency mismatch between applied stimulation and individual alpha frequency (IAF) and as a covariate, subject’s changes in mental state, i.e., sleepiness. Eighteen subjects participated in a tACS and a sham session conducted on different days. Each session consisted of three runs (pre/stimulation/). tACS was applied during the second run at each subject’s individual alpha frequency (IAF), applying 1 mA peak-to-peak intensity for 7 min, using an occipital bihemispheric montage. In every run, subjects watched a video designed to increase in-scanner compliance. To investigate the aftereffect of tACS on EEG alpha amplitude and on DMN connectivity strength, EEG data were recorded simultaneously with fMRI data. Self-rated sleepiness was documented using a questionnaire. Conventional statistics (ANOVA) did not show a significant aftereffect of tACS on the alpha amplitude compared to sham stimulation. Including individual EFIELD strengths and self-rated sleepiness scores in a multiple linear regression model, significant tACS-induced aftereffects were observed. However, the subject-wise mismatch between tACS frequency and IAF had no contribution to our model. Neither standard nor extended statistical methods confirmed a tACS-induced aftereffect on DMN functional connectivity. Our results show that it is possible and necessary to disentangle alpha amplitude changes due to intrinsic mechanisms and to external manipulation using tACS on the alpha amplitude that might otherwise be overlooked. Our results suggest that EFIELD is really the most significant factor that explains the alpha amplitude modulation during a tACS session. This knowledge helps to understand the variability of the tACS-induced aftereffects.
Effects of Oral Multi-Vitamin Multi-Mineral Supplement Formulations on Laboratory Outcomes and Quality of Life: A Quasi-Experimental Study
Authors: Jittat Nawin , Pongpirul Krit , Tepwituksakit Bhakanij , Iammaleerat Pratchayada , Heath Julia , Lungchukiet Palita , Taechakraichana Nimit , Charukitpipat Artirat
Published: June 2022

Background

Multi-vitamin multi-mineral (MVMM) products often come in several single-substance capsules from different manufacturers. However, attempts to mix several vitamins and minerals into one MVMM product have been complicated and often involve legal concerns. This study aimed to comparatively investigate the changes in laboratory parameters and the quality of life (QOL) among individuals who received different MVMM formulations.

Methods

This three-arm non-randomized controlled trial was conducted at VitalLife Scientific Wellness Center (VSWC), Bangkok, Thailand. A total of 72 healthy adult individuals with total serum 25-(OH)D level of 20–29 ng/ml were invited to choose from the three available options, namely, (1) Hydro-Cell-Key (HCK®, Hepart AG, Switzerland) contains vitamin D3 2,000 IU, vitamin C 1,000 mg, vitamin E 166 mg, vitamin A 1 mg, coenzyme Q10 30 mg, natural carotenoids 8 mg, and citrus flavonoids 200 mg in granule formulation; (2) VTL-7 (VWSC) contains similar vitamins and minerals but in capsule formulation; and (3) placebo capsule (no supplement). The 36-Item Short-Form Health Survey (SF-36) was used to measure QOL at baseline, month 3 and 6. A generalized estimating equation (GEE) was used to compare the repeated-measure outcomes across the three groups. This study was registered at the Thai Clinical Trial Registration (TCTR20190205002) and approved by the Bumrungrad International Institutional Review Board (BI-IRB No.258-10-18PhFub).

Results

Both VTL-7 and HCK saw a significantly higher increase in vitamin D than placebo at months 3 and 6, i.e., VTL-7 from 25.15 ± 2.13 to 35.53 ± 6.11 (p < 0.001) and 33.38 ± 6.89 (p < 0.001); HCK from 24.25 ± 3.08 to 28.43 ± 5.93 (p = 0.005) and 27.40 ± 5.24 (p = 0.012); and placebo from 24.00 ± 2.73 to 23.05 ± 4.39 (p = 0.273) and 22.30 ± 6.23 (p = 0.200), respectively. Similarly, β-carotenoids of VTL-7 vs. HCK groups significantly increased from 0.88 ± 0.68 vs. 0.94 ± 0.55 at baseline to 3.03 ± 1.79 (p < 0.001) vs. 1.09 ± 0.61 (p = 0.125) and 3.26 ± 1.74 (p < 0.001) vs. 1.15 ± 0.66 (p = 0.064), respectively. These findings were corroborated through the GEE analysis. Other micronutrients at months 3 and 6 did not increase significantly from baseline in any group. The overall QOL among the three groups in terms of physical (p = 0.560) and mental (p = 0.750) health increased but was not statistically significant.

Conclusion

The supplements of MVMM in capsule formulation increased the serum levels of some micronutrients to a higher extent than that of granule formulation. Participant adherence remains a potential confounder and should be further explored.

Clinical Trial Registration

identifier: TCTR20190205002.
Development of a Prognostic Alternative Splicing Signature Associated With Tumor Microenvironment Immune Profiles in Lung Adenocarcinoma
Authors: Bao Guangyao , Li Tian , Guan Xiaojiao , Yao Yao , Liang Jie , Xiang Yifan , Zhong Xinwen
Published: June 2022

Background

Alternative splicing (AS), a pivotal post-transcriptional process across more than 95% of human transcripts, is involved in transcript structural variations and protein complexity. Clinical implications of AS events and their interaction with tumor immunity were systematically analyzed in lung adenocarcinoma (LUAD).

Methods

Transcriptome profiling as well as AS data of LUAD were retrospectively curated. Then, the network of the overall survival (OS)-relevant AS events with splicing factors was established. After screening OS-relevant AS events, a LASSO prognostic model was conducted and evaluated with ROC curves. A nomogram that integrated independent prognostic indicators was created. Immune response and immune cell infiltration were estimated with ESTIMATE, CIBERSORT, and ssGSEA algorithms. Drug sensitivity was inferred with pRRophetic package.

Results

In total, 2415 OS-relevant AS events were identified across LUAD patients. The interaction network of splicing factors with OS-relevant AS events uncovered the underlying regulatory mechanisms of AS events in LUAD. Thereafter, a prognostic model containing 12 AS events was developed, which acted as a reliable and independent prognostic indicator following verification. A nomogram that constituted stage and risk score displayed great effectiveness in evaluating the survival likelihood. Moreover, the AS-based prognostic model was in relation to immune response and immune cell infiltration. Patients with a high-risk score displayed therapeutic superiority to cisplatin, erlotinib, gefitinib, and gemcitabine. Finally, three AS-relevant genes (CDKN2A, TTC39C, and PKIB) were identified as prognostic markers.

Conclusion

Collectively, our findings developed an AS event signature with powerful prognostic predictive efficacy in LUAD.
Clinical Outcome After Pencil Beam Scanning Proton Therapy of Patients With Non-Metastatic Malignant and Benign Peripheral Nerve Sheath Tumors
Authors: Bachmann Nicolas , Leiser Dominic , Pica Alessia , Bachtiary Barbara , Weber Damien C.
Published: June 2022

Objective

Peripheral nerve sheath tumors (PNSTs) commonly arise from peripheral nerve roots and grow locally invasive. Malignant PNSTs (mPNSTs) represent aggressive sarcomas of neural origin that can originate from PNSTs. Radiation therapy is commonly used as part of the required multimodal treatment. However, both entities tend to occur early in life and are associated with the genetic disorder neurofibromatosis type 1 (NF-1), which is known to cause increased radiosensitivity. Pencil beam scanning proton therapy (PBSPT) allows for a minimization of the dose delivered to organs at risk and the integral dose and, thus, potentially also a reduction of radiation-induced adverse events. We report the clinical outcome and toxicity rates of patients with (m)PNSTs treated with PBSPT.

Methods

We retrospectively reviewed 36 patients who received PBSPT (median dose, 64 GyRBE) with curative intent for (m)PNSTs between 1999 and 2020 at our institute. Twenty-eight (78%) and 8 (22%) patients were treated at diagnosis and for tumor recurrence/progression, respectively. The median age was 32 years (range, 3–75), and 25 (69%) patients were male. mPNST and PNST were diagnosed in 31 (86%) and 5 (14%) patients, respectively. Underlying NF-1 disease was found in 8 (22%) patients. Acute and late toxicities were recorded according to Common Terminology Criteria for Adverse Events, version 4.1 (CTCAE v4.1). Overall survival (OS), local control (LC), and distant control (DC) were estimated using the Kaplan–Meier method.

Results

With a median follow-up time of 31 months (range, 4–194), 13 (36%) patients died from a progressive disease, 8 (22%) experienced local failure, and 14 (39%) experienced distant failure after PBSPT. Estimated 2-year OS, LC, and DC were 75.5%, 73.5%, and 61.2%, respectively. Acute grade 3 toxicity (dermatitis, mucositis, and pain) was observed in 5 (14%) patients. Late grade 3 cataract and osteonecrosis were both observed in 1 (3%) patient at 34 and 194 months after PBSPT, respectively. There was no late grade >3 toxicity or radiation-induced secondary cancer.

Conclusion

To our knowledge, this is the first study to analyze the outcome of (m)PNSTs treated with proton therapy using a PBS delivery paradigm. In our cohort, consisting mainly of patients with mPNSTs, we report reasonable oncological outcomes and low toxicity rates after PBSPT.
The Prevalence of Glaucoma in the Jirel Ethnic Group of Nepal
Authors: Miller Sarah , Blackburn Nicholas B. , Johnson Matthew , Laston Sandra , Subedi Janardan , Charlesworth Jac C. , Blangero John , Towne Bradford , Thapa Suman S. , Williams-Blangero Sarah
Published: June 2022

Glaucoma is one of the leading causes of blindness worldwide with individuals in Asia disproportionately affected. Using a cross-sectional study design as part of the Jiri Eye Study, we assessed the prevalence of glaucoma in the Jirel population of Nepal and provide new information on the occurrence of glaucoma in south central Asia. Over a four-year period, 2,042 members of the Jirel population, aged 18 years and older, underwent a detailed ocular examination. Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology criteria. The mean (SD) age at exam was 42.3 (16.7) years and 54.1% of the sample was female. In the total sample, the mean (SD) intraocular pressure (IOP) and vertical cup-to-disc ratio (VCDR) was 14.55 (2.42) mmHg and 0.31 (0.15), respectively. The 97.5th and 99.5th percentile for IOP and VCDR was 20 mmHg and 22 mmHg, and 0.7 and 0.8, respectively. The overall prevalence of glaucoma in the population was 2.30% (n = 47). Of these 47 individuals, 37 (78.7%) had primary open angle glaucoma, 6 (12.8%) had primary angle closure glaucoma, and 4 (8.5%) had secondary glaucoma. There was a significant (p = 5.86×10−6) increase in the prevalence of glaucoma with increasing age overall and across glaucoma subtypes. Six individuals with glaucoma (12.8%) were blind in at least one eye. Of the individuals with glaucoma, 93.6% were previously undiagnosed. In individuals aged 40 years or older (n = 1057, 51.4% female), the mean (SD) IOP and VCDR was 14.39 (2.63) mmHg and 0.34 (0.16), respectively, and glaucoma prevalence was 4.16% (n = 44). The prevalence of glaucoma and undiagnosed disease is high in the Jirel population of Nepal. This study will inform strategies to minimize glaucoma-associated burden in Nepal.
Characteristics and Regulating Roles of Wheat TaHsfA2-13 in Abiotic Stresses
Authors: Meng Xiangzhao , Zhao Baihui , Li Mingyue , Liu Ran , Ren Qianqian , Li Guoliang , Guo Xiulin
Published: June 2022

Heat shock transcription factor (Hsf) exists widely in eukaryotes and responds to various abiotic stresses by regulating the expression of downstream transcription factors, functional enzymes, and molecular chaperones. In this study, TaHsfA2-13, a heat shock transcription factor belonging to A2 subclass, was cloned from wheat (Triticum aestivum) and its function was analyzed. TaHsfA2-13 encodes a protein containing 368 amino acids and has the basic characteristics of Hsfs. Multiple sequence alignment analysis showed that TaHsfA2-13 protein had the highest similarity with TdHsfA2c-like protein from Triticum dicoccoides, which reached 100%. The analysis of tissue expression characteristics revealed that TaHsfA2-13 was highly expressed in root, shoot, and leaf during the seedling stage of wheat. The expression of TaHsfA2-13 could be upregulated by heat stress, low temperature, H2O2, mannitol, salinity and multiple phytohormones. The TaHsfA2-13 protein was located in the nucleus under the normal growth conditions and showed a transcriptional activation activity in yeast. Further studies found that overexpression of TaHsfA2-13 in Arabidopsis thaliana Col-0 or athsfa2 mutant results in improved tolerance to heat stress, H2O2, SA and mannitol by regulating the expression of multiple heat shock protein (Hsp) genes. In summary, our study identified TaHsfA2-13 from wheat, revealed its regulatory function in varieties of abiotic stresses, and will provide a new target gene to improve stress tolerance for wheat breeding.
Genome-Wide Expression Analysis of Glyoxalase I Genes Under Hyperosmotic Stress and Existence of a Stress-Responsive Mitochondrial Glyoxalase I Activity in Durum Wheat (Triticum durum Desf.)
Authors: Soccio Mario , Marangi Marianna , Laus Maura N.
Published: June 2022

Glyoxalase I (GLYI) catalyzes the rate-limiting step of the glyoxalase pathway that, in the presence of GSH, detoxifies the cytotoxic molecule methylglyoxal (MG) into the non-toxic D-lactate. In plants, MG levels rise under various abiotic stresses, so GLYI may play a crucial role in providing stress tolerance. In this study, a comprehensive genome database analysis was performed in durum wheat (Triticum durum Desf.), identifying 27 candidate GLYI genes (TdGLYI). However, further analyses of phylogenetic relationships and conserved GLYI binding sites indicated that only nine genes encode for putative functionally active TdGLYI enzymes, whose distribution was predicted in three different subcellular compartments, namely cytoplasm, plastids and mitochondria. Expression profile by qRT-PCR analysis revealed that most of the putative active TdGLYI genes were up-regulated by salt and osmotic stress in roots and shoots from 4-day-old seedlings, although a different behavior was observed between the two types of stress and tissue. Accordingly, in the same tissues, hyperosmotic stress induced an increase (up to about 40%) of both GLYI activity and MG content as well as a decrease of GSH (up to about –60%) and an increase of GSSG content (up to about 7-fold) with a consequent strong decrease of the GSH/GSSG ratio (up to about –95%). Interestingly, in this study, we reported the first demonstration of the existence of GLYI activity in highly purified mitochondrial fraction. In particular, GLYI activity was measured in mitochondria from durum wheat (DWM), showing hyperbolic kinetics with Km and Vmax values equal to 92 ± 0.2 μM and 0.519 ± 0.004 μmol min–1 mg–1 of proteins, respectively. DWM–GLYI resulted inhibited in a competitive manner by GSH (Ki = 6.5 ± 0.7 mM), activated by Zn2+ and increased, up to about 35 and 55%, under salt and osmotic stress, respectively. In the whole, this study provides basis about the physiological significance of GLYI in durum wheat, by highlighting the role of this enzyme in the early response of seedlings to hyperosmotic stress. Finally, our results strongly suggest the existence of a complete mitochondrial GLYI pathway in durum wheat actively involved in MG detoxification under hyperosmotic stress.
Effects of 15-Days −6° Head-Down Bed Rest on the Attention Bias of Threatening Stimulus
Authors: Jiang Shan , Qian YI-Ming , Jiang Yuan , Cao Zi-Qin , Xin Bing-Mu , Wang Ying-Chun , Wu Bin
Published: June 2022

Previous researchers have found that head-down bed rest (HDBR) will affect the emotional state of individuals, and negative emotions such as anxiety are closely related to attention bias. The present study adopted the dot-probe task to evaluate the effects of 15-days of −6° HDBR on the attention bias of threatening stimulus in 17 young men, which was completed before (Pre-HDBR), during (HDBR-1, HDBR-8, HDBR-15), after (Post-HDBR) the bed rest. In addition, self-report inventories (State Anxiety Inventory, SAI; Positive Affect and Negative Affect Scale, PANAS) were conducted to record emotional changes. The results showed that the participants’ negative affect scores on HDBR-8 were significantly lower than the HDBR-1 in PANAS while there was no significant difference on positive affect scores and anxiety scores in SAI. And the results showed that at the Pre-HDBR, HDBT-1, HDBR-15, Post-HDBR, the response speed to threatening stimulus was faster than neutral stimulus, but no statistical significance. However, reaction time of threatening stimulus is significantly longer than neutral stimulus in the HDBR-8, indicating that HDBR may have an effect on the participants’ attention bias, and this effect is manifested as attention avoidance.
Translation, Cross-Cultural Adaptation, and Psychometric Testing of Yoruba Version of the EQ-5D Questionnaire in Patients With Musculoskeletal Disorders
Authors: Fatoye Francis , Akinfala Abiodun Emmanuel , Gebrye Tadesse , Fatoye Clara , Ojelade Titilope Faith , Oyewole Olufemi Oyeleye , Mbada Chidozie Emmanuel
Published: June 2022

Background

The EuroQol-5 Dimension (EQ-5D) is a generic self-administered questionnaire used for the measurement and economic valuation of a wide range of health conditions, which necessitates its existence and adaptation in different languages. Currently, the tool does not exist in any Nigerian language. This study aimed to translate, cross-culturally adapt, and determine the reliability and validity of the Yoruba version of the EQ-5D-5L questionnaire.

Methods

The International Quality of Life Assessment (IQOLA) project guidelines, involving forward translation, reconciliation and harmonization, backward translation, and reconciliation of problematic items were used in the Yoruba translated version of the EQ-5D-5L (EQ-5D-Yor). A total of 113 and 109 persons with musculoskeletal disorders participated in the validity and 7-day test-retest reliability testing of the EQ-5D-Yor. Convergent and discriminant validity of the EQ-5D-Yor were determined using the Yoruba version of the 12-Item Short-Form Health Survey (SF-12) (SF-12-Y) and Visual Analog Scale (VAS). Data were analyzed using descriptive and inferential statistics of Spearman correlation, Intra-Class Correlation, Cronbach alpha, and multi-trait scaling analysis. Alpha level was set as p < 0.05.

Results

The construct validity of the EQ-5D-Yor yielded Spearman rho ranging from 0.438 to 1.000, with the EQ-VAS having the highest co-efficient (r = 1.000; p = 0.001). The convergent validity of the EQ-5D-Yor index with scales and domains of the SF-12-Y yielded no significant correlations (p < 0.05), except for the physical functioning scale (r = −0.709, p = 0.001). On the other hand, the divergent validity of the EQ-5D-Yor index with VAS yielded a moderate negative correlation (r = −0.482; p = 0.001). The Intra-class Correlation Coefficient (ICC) and Cronbach's alpha for the test-retest reliability of the EQ-5D-Yor were 1.000 and 0.968. The confirmatory factor analysis showed the factor loadings were poor when including VAS in the model.

Conclusion

The EQ-5D-Yor has acceptable validity and reliability and can be used as a valid tool among Yoruba speaking population with musculoskeletal disorders.
Shaping the Qualities, Values and Standards of Science. How Reporting Guidelines Improve the Transparency of Biomedical Research
Authors: Schniedermann Alexander
Published: June 2022

What is scientific quality and how can it be achieved? Recent developments in clinical biomedicine gave prominence to transparency as a new core value for scientific research. Without transparency, other characteristics and values remain unknown. But how can abstract concepts and values be implemented in day-to-day scientific practices and what gets lost on the way? In order to answer this question, this study investigates the role of the PRISMA reporting guideline for writing systematic reviews and meta-analyses. By combining a document analysis and expert interviews with its developers, it attempts to bridge the gap between research practice and current modes of evaluation. Beside showing how the guideline was designed to be applicable and acceptable as a new standard, the analysis revealed crucial distinctions between transparency as an abstract quality goal and its practical implementation in the form of specifically formulated rules. Although PRISMA relies on transparency in order to be meaningful, it blurs the concept in order to circumvent some of its main disadvantages.