bluuebunny/crossref_metadata_2025 huggingface dataset:
Hubungan Pola Asuh Orang Tua Dengan Perkembangan Sosial Dan Kemandirian Fisik Anak Usia Prasekolah 4-6 Tahun Di Taman Kanak-Kanak Wilayah Meruyung Kota Depok
Authors: Nabila Putri Aulia , Sukamti Nita , Usman Andi Mayasari
Published: April 2022

ABSTRACT In developed countries 50% of preschool children aged show anti social behavior disorders. The prevalence of independence level is 53% independent, 9% dependent on parents, 38% fully dependent on parents and 17% quite independent. If it abandoned, behavioral disorder and independence will occur. This research was aimed to determine the relationship of parenting styles with social development and physical independence on preschool children. This research method used a descriptive analysis design with a cross sectional approach. The sample was 50 respondents. Sampling technique with total sampling. The research instrument used a questionnaire. The data were analyzed using a non-parametric test, namely chi square. The research results of the 50 parent respondents who applied democratic parenting were 22 respondents (44.0%) with good social development of 27 respondents (54.0%) and less physical independence was 25 respondents (50.0%). The parenting result with social development obtained p value = 0.001 (p < 0.05) and parenting with physical independence p value = 0.001 (p < 0.05). There is a relationship of parenting style with social development and independence in preschool children aged 4-6 years in Kindergarten at Meruyung Region, Depok City. Keywords: Parenting Style, Social Development, Physical Independence ABSTRAK Negara maju 50% anak usia prasekolah menunjukan gangguan perilaku anti sosial. Prevalensi tingkat kemandirian 53% mandiri, 9% bergantung orang tua, 38% bergantung penuh dengan orang tua dan 17% cukup mandiri. Jika didiamkan akan terjadi gangguan perilaku dan ketidakmandirian. Penelitian ini bertujuan untuk mengetahui hubungan pola asuh orang tua dengan perkembangan sosial dan kemandirian fisik anak usia prasekolah. Metode penelitian ini menggunakan desain deskriptif analisis dengan pendekatan cross sectional. Sampel berjumlah 50 responden. Teknik pengambilan sampel dengan total sampling. Instrumen penelitian ini menggunakan kuesioner. Data dianalisis menggunakan uji non parametrik yaitu chi square. Hasil penelitian dari 50 responden orang tua menerapkan pola asuh demokratis sebanyak 22 responden (44,0%) dengan perkembangan sosial cukup baik 27 responden (54,0%) dan kemandirian fisik kurang mandiri yaitu 25 responden (50,0%). Hasil pola asuh dengan perkembangan sosial didapatkan nilai p= 0,001 (p<0,05) dan pola asuh dengan kemandirian fisik nilai p= 0,001 (p<0,05). Terdapat hubungan pola asuh dengan perkembangan sosial dan kemandirian pada anak usia prasekolah 4-6 tahun  di Taman Kanak-kanak Wilayah Meruyung Kota Depok. Kata Kunci : Pola Asuh Orang tua, Perkembangan Sosial, Kemandirian Fisik
La didactique de l’Information-Documentation en France comme ressource pour l'enseignement : une histoire et une "épistémologie plurielle"
Authors: Frisch muriel
Published: April 2022

Information-Documentation didactic in France as teaching resources: an history and a “plural epistemology”. This text is based on our research Information-Documentation didactic. It focuses on the epistemological and historical dimensions developed in our Habilitation Thesis (2016) and uses a review of the literature. This paper is thus going to be organized into four parts: characterization of what we call a “plural epistemology”; origins and history of Documentation-Information training in Education; neighboring fields, complementary and identification of trends, paradigms and models dominant; documentary culture, Information-Documentation didactic and link with teaching of history.
Hr-management business processes digitalization: hrm-systems possibilities
Authors: Varis I. , Kravchuk O. , Parashchuk Ye.
Published: April 2022

Digitalization of business processes of personnel management is investigated in this paper. The digital transformation of personnel management has changed the company’s business processes, created a digital work environment, and introduced modern digital technologies. Therefore, it is important to identify modern ways of digitizing business processes of personnel management by using HRM-systems, as well as identify their functionality and capabilities. Digital transformation of business processes in HR management through social, mobile, analytical and cloud technologies allows to optimize work with paper documents, improve procedures and operations of personnel management, reduce their complexity, make all HR activities more mobile. This makes it possible not only to improve the involvement and retention of employees, but also significantly increase the success of the company through continuous transformation, which is important for business as a whole. Capabilities of modern domestic and foreign HRM-systems are analyzed and their advantages and disadvantages are identified in this paper. Comparative analysis of modern HRM-systems allows to generalize the possibilities for automating personnel management’s main business processes. Recommendations for evaluating the effectiveness of HRM-systems into practice of modern company’s personnel management are proposed. Key areas and indicators that characterize the features of software for personnel management automation are identified. Implementation of the initiative on digital transformation of HR-processes is an important task for enterprises. In practice, it is crucial issue to have an assessment of the real picture for digitization process and its effectiveness. The digitalization of personnel management’s business processes involves the usage of platforms for personnel, which offer functionality to automate many HR processes. Companies use HRM-systems, which allow managing key HR-functions within centralized system that optimizes personnel management’s business processes and reporting. HRM systems are the most important applications used in companies of all sizes and in all types of economic activities. The methods and the ways for evaluating the effectiveness of HR-processes’ digitization are not yet sufficiently investigated, which in turn, gives prospects for further research in this area.
The shifting trend in online buyer's behaviour under the impact of COVID-19 pandemic in Vietnam
Authors: Nguyen Ha Thu , Hoang Thuy Dam Luong , Nguyen Huy Khanh
Published: April 2022

COVID-19 temporarily hindered the development of physical stores, nevertheless, triggered the outbreak of online business. Consequently, there should be growing demands for purchasing over internet-based platform. In order to investigate online purchase intention and online shopping behaviour, this study developed a research framework basing on the analysis of 05 different variables, namely: subjective norm, attitude, behavioural control, trust, and perceived risk. A sample of 307 Vietnamese online customers have been surveyed, resulting to the findings that behavioural control and trust have direct influence on online purchase intention, then indirectly generates online shopping behaviour. Especially, trust is considered to have the greatest effects, followed by behavioural control. From the results, implications can be established about marketing implementation in online shopping service. In other words, marketing campaigns for COVID-19 context is aimed at highly productive purposes in order to coping with epidemic time.
A new perspective of brand equity: the case of pottery craft village collective brand in Vietnam
Authors: Van Ngo Quang , Vu Ha Thu Thi
Published: April 2022

Brand equity is one of the most critical factors that significantly affect the success of any business. With 860 samples, this study indicates that the brand equity of a collective Vietnamese pottery craft village is constituted by four factors, including brand awareness, brand association, perceived quality, and brand loyalty. Particularly, brand awareness has the strongest and most positive impact on the pottery village collective brand equity. This study is a way to confirm the difference between brand awareness and brand association (two variables are measured by independent scales), therefore, it is impossible to combine these two variables in testing and measuring brand equity as done by controversial studies in recent years. This study has revealed that “age” contributes as the regulatory moderation impacts the relationship between brand awareness, brand association, perceived quality, brand loyalty and collective brand equity of pottery craft village. This research also has proposed suggestions to help the pottery village collective brand owner increase their brand value.
Methods and forms of digital learning with distance education technologies: Opinions and preferences of students at the institutes of culture
Authors: Mukhametshin R. R.
Published: April 2022

The author continues to review the attitude of students in the speciality “Library information activities” toward methods and formats of digital learning through distance education technologies. The students of educational institutions of the RF Ministry of Culture were surveyed. Three hundred and eighty three (383) bachelor-program students and 65 masters-to-be participated in the survey. The respondents specified the methods and format of digital learning introduced during the restriction pandemic period. It is demonstrated that after these emasures had been introduced, the intensity of utilization of digital learning methods and forms increased, as well as the ratio of the so-called external methods and forms, i. e. messengers and videoconference systems. It is established that the learners prefer the systems and/or services that they know and are used to. At the same time, the dynamics of moving toward solutions integrated into digital information education environment is demonstrated. The author argues that almost every digital information education environment features some kinds of external methods and forms of digital learning with distance education technologies. The results of their application can be preserved and replicated. To make their digital learning with distance education technologies more efficient, educational institutions have to minimize external systems and look into possibility of introducing mass open online courses.
Problematika Perbedaan Nilai Kriteria Ketuntasan Minimal (KKM) Mata Pelajaran Pendidikan Agama Islam dan Budi Pekerti Pada Kurikulum 2013 (Studi kasus di SMK Muhammadiyah 1 Ciputat Tangerang Selatan)
Authors: Yuniarsih Wiguna , Syarif Fajar , Fahruroji Fahruroji
Published: April 2022

The purpose of this study was to describe the difference in KKM scores between majors/skills programs, as well as the inhibiting and supporting factors in Islamic religious education subjects at SMK Muhammadiyah 1 Ciputat, South Tangerang. This study used qualitative research methods. Data collection techniques through observation, interviews, and documentation. While the data analysis technique used descriptive analysis. The results of this study indicate that; 1) The difference in the KKM value of each department with the smallest KKM value of each marketing department is the KKM value for class X 77.67, XI 70.33 and XII 70.33. While the highest KKM value is in the accounting department with a KKM value of class X 80.67, XI 75.67 and XII 76.67. 2) Supporting factors include facilities and infrastructure as well as teachers who master the learning material. While the inhibiting factor is the level of intelligence of students who are different so that the assessment of PAI and BP subjects does not reach the KKM.
Nucleic Acid Sensing Pathways in DNA Repair Targeted Cancer Therapy
Authors: Xie Bingteng , Luo Aiqin
Published: April 2022

The repair of DNA damage is a complex process, which helps to maintain genome fidelity, and the ability of cancer cells to repair therapeutically DNA damage induced by clinical treatments will affect the therapeutic efficacy. In the past decade, great success has been achieved by targeting the DNA repair network in tumors. Recent studies suggest that DNA damage impacts cellular innate and adaptive immune responses through nucleic acid-sensing pathways, which play essential roles in the efficacy of DNA repair targeted therapy. In this review, we summarize the current understanding of the molecular mechanism of innate immune response triggered by DNA damage through nucleic acid-sensing pathways, including DNA sensing via the cyclic GMP-AMP synthase (cGAS), Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2), DNA-dependent protein kinase (DNA-PK), and Mre11-Rad50-Nbs1 complex (MRN) complex, and RNA sensing via the TLR3/7/8 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Furthermore, we will focus on the recent developments in the impacts of nucleic acid-sensing pathways on the DNA damage response (DDR). Elucidating the DDR-immune response interplay will be critical to harness immunomodulatory effects to improve the efficacy of antitumor immunity therapeutic strategies and build future therapeutic approaches.
Smoking in Patients With Chronic Cardiovascular Disease During COVID-19 Lockdown
Authors: Chagué Frédéric , Boulin Mathieu , Eicher Jean-Christophe , Bichat Florence , Saint-Jalmes Maïlis , Cransac Amélie , Soudry Agnès , Danchin Nicolas , Laurent Gabriel , Cottin Yves , Zeller Marianne
Published: April 2022

Objectives

This cross-sectional study aims to investigate health-related behaviors including tobacco consumption among patients with cardiovascular diseases (CVD), during the first COVID-19-related lockdown.

Methods

After 5 weeks of COVID-19 lockdown, 220 patients with chronic coronary syndromes (CCS) and 124 with congestive heart failure (CHF) answered a phone questionnaire.

Results

Among these 344 patients, 43 (12.5%) were current smokers, and none had quit during the lockdown. When compared with non-smokers, smokers were 15 years younger, more often diabetic, more likely to live in an urban than a rural lockdown location, and more often in the CCS cohort (p = 0.011). Smokers described greater psychological impairment, but their rates of decrease in physical activity and of increase in screen time were similar to non-smokers. More than one-third (13/43) increased their tobacco consumption, which was mainly related to stress or boredom, but not driven by media messages on a protective effect of nicotine.

Conclusions

During the first COVID-19 lockdown, we found a decrease in favorable lifestyle behaviors among patients with CVD. Strikingly, one-third of smokers with CCS or CHF increased their tobacco consumption. Given the major impact of persistent smoking in patients with CVD, this highlights the need for targeted prevention strategies, in particular during such periods.
Non-alcoholic Fatty Liver Disease Is Associated With Cardiovascular Outcomes in Subjects With Prediabetes and Diabetes: A Prospective Community-Based Cohort Study
Authors: Song Qi-Rui , Liu Shuo-Lin , Bi Ya-Guang , Chen Shuo-Hua , Wu Shou-Ling , Cai Jun
Published: April 2022

Background

There have been no studies of the effect of non-alcoholic fatty liver disease (NAFLD) on cardiovascular events (CVEs) in patients with pre-diabetes (pre-DM), and diabetes mellitus (DM). We performed a community-based cohort study to evaluate the relationship between NAFLD and CVEs in patients with glucose metabolism disorder.

Methods

We enrolled 71,852 participants from the Kailuan study who had not experienced CVEs, after excluding alcohol abuse and other liver diseases. NAFLD was assessed using abdominal ultrasonography. Besides, participants were categorized by glucose metabolism status [normal glucose regulation (NGR), pre-DM, and DM]. All subjects were followed up for the occurrence of CVEs.

Results

During a median of 13.01 (0.64) years of follow-up, 6,037 CVEs occurred. NAFLD was present in 22,525 (31.3%), and compared with participants without NAFLD, those with NAFLD had a 12.3% [95% confidence interval (CI) 1.059–1.191, P < 0.001] higher risk of CVEs, after adjustment for potential confounders. The hazard ratios for patients with mild, moderate, and severe NAFLD were 1.104 (95% CI 1.035–1.179, P < 0.001), 1.149 (95% CI 1.055–1.251, P < 0.001), and 1.235 (95% CI 1.059–1.441, P < 0.001), respectively. Moreover, participants with pre-DM plus NAFLD and participants with DM plus NAFLD had 1.267-fold (95% CI 1.151–1.395, P < 0.001) and 1.829-fold (95% CI 1.666–2.008, P < 0.001) higher risks of CVEs, respectively, compared with those with NGR and no NAFLD. The addition of the combination of NAFLD and glucose metabolism status to the crude Cox model increased the C-statistic by 0.0066 (0.0053–0.0080, P < 0.001).

Conclusions

NAFLD is associated with higher risks of CVEs. Moreover, NAFLD is an independent predictor of CVEs in patients with pre-DM and DM, suggesting that NAFLD may provide greater risk predictive value for patients with glucose metabolism disorder.
Identifying Pupylation Proteins and Sites by Incorporating Multiple Methods
Authors: Qiu Wang-Ren , Guan Meng-Yue , Wang Qian-Kun , Lou Li-Liang , Xiao Xuan
Published: April 2022

Pupylation is an important posttranslational modification in proteins and plays a key role in the cell function of microorganisms; an accurate prediction of pupylation proteins and specified sites is of great significance for the study of basic biological processes and development of related drugs since it would greatly save experimental costs and improve work efficiency. In this work, we first constructed a model for identifying pupylation proteins. To improve the pupylation protein prediction model, the KNN scoring matrix model based on functional domain GO annotation and the Word Embedding model were used to extract the features and Random Under-sampling (RUS) and Synthetic Minority Over-sampling Technique (SMOTE) were applied to balance the dataset. Finally, the balanced data sets were input into Extreme Gradient Boosting (XGBoost). The performance of 10-fold cross-validation shows that accuracy (ACC), Matthew’s correlation coefficient (MCC), and area under the ROC curve (AUC) are 95.23%, 0.8100, and 0.9864, respectively. For the pupylation site prediction model, six feature extraction codes (i.e., TPC, AAI, One-hot, PseAAC, CKSAAP, and Word Embedding) served to extract protein sequence features, and the chi-square test was employed for feature selection. Rigorous 10-fold cross-validations indicated that the accuracies are very high and outperformed its existing counterparts. Finally, for the convenience of researchers, PUP-PS-Fuse has been established at https://bioinfo.jcu.edu.cn/PUP-PS-Fuse and http://121.36.221.79/PUP-PS-Fuse/as a backup.
Quantifying Stimulus-Affected Cinematic Spaces Using Psychophysiological Assessments to Indicate Enhanced Cognition and Sustainable Design Criteria
Authors: Sakhaei Hamidreza , Yeganeh Mansour , Afhami Reza
Published: April 2022

Objectives: Converging architecture with cinema and cognition has proved to be a practical approach to scrutinizing architectural elements’ significant contribution to engineering science. In this research, a behavioral analysis has been conducted to examine if disruptive events in cinematic spaces can lead to an insightful perception of architectural qualities and enhanced interplay with the observed spaces to highlight mental health and improved cognitive tasks in sustainable design characteristics.

Methods: The experiment was conducted in participants (N = 90) while watching three films with different stimuli to facilitate multivariate analyses. The HR, BP, SCL, and BT were measured while screening films to subjects. Psychological assessments of PANAS, TIPI, Chills, Pleasure, Arousal, Dominance, and NAQ were gathered to conduct correlation and regression analyses between variables. An independent space syntax analysis of film plans was also performed to compare film spaces’ properties.

Results: Analyses show that physiological responses of HR, BP, SCL, and BT showed a meaningful relationship with the event intensity. Psychological assessments of Chills, SAM, and NAQ also depicted a meaningful relationship with the degree of stimuli during the movie screenings. Regression analyses illustrated that the age factor had a significant relationship with Arousal (p-value = 0.04), Chills (p-value = 0.03), and Dominance (p-value = 0.00). The TIPI factor showed a meaningful relationship with Chills (p-value = 0.03) and Dominance (p-value = 0.00). PANAS PA factor’s relationship was significant on Chills (p-value = 0.00), Arousal (p-value = 0.04), and Dominance (p-value = 0.03), and the PANAS NA factor showed a meaningful relationship with Chills (p-value = 0.00) and Dominance (p-value = 0.05). The correlations in Chills–Arousal (p-value = 0.01), PANAS NA–TIPI (p-value = 0.01), NAQ–Pleasure (p-value = 0.05), and Arousal–Dominance (p-value = 0.00) were significant. Space syntax analyses also showed that film 3 had a mixed plan structure than the other two films. Factors such as area compactness, connectivity, visual entropy, controllability, and mean depth were influential in distinguishing film spaces.

Conclusion: It has been concluded that the space with intensive disruption of architectural elements successfully indicated improved cognitive perception of spatial qualities, enhanced interaction, and signified sustainable design criteria. Evoking events disrupted the banalization of cinematic spaces, illustrating that the designed model can indicate a more homogenous evaluation of a sustainable environment.
Biotechnological Applications of Manganese Peroxidases for Sustainable Management
Authors: Kumar Ashish , Arora Pankaj Kumar
Published: April 2022

Microbial manganese peroxidases (MnPs) are ligninolytic enzymes primarily responsible for degrading lignin, but they are also capable of degrading dyes, organic pollutants, and emerging contaminants in wastewater. They have been isolated and characterized from many white-rot fungi and few bacteria. For microbial MnPs, the optimum pH range is between 3.5 and 9.0; the optimum temperature range is between 25°C and 70°C. Their molecular weights range between 25 kDa and 68 kDa. By oxidizing Mn2+ to Mn3+, they can oxidize a wide range of phenolic and non-phenolic substrates. MnPs can be used in a wide range of industrial applications, including delignification of pulp, wastewater treatment, biofuel production, dye removal, biopulping, biobleaching, and juice extract clarification. The purpose of this review is to summarize biotechnological applications of manganese peroxidases.
The Island of Female Power? Intersexual Dominance Relationships in the Lemurs of Madagascar
Authors: Kappeler Peter M. , Fichtel Claudia , Radespiel Ute
Published: April 2022

The extant primates of Madagascar (Lemuriformes) represent the endpoints of an adaptive radiation following a single colonization event more than 50 million years ago. They have since evolved a diversity of life history traits, ecological adaptations and social systems that rivals that of all other living primates combined. Their social systems are characterized by a unique combination of traits, including the ability of adult females to dominate adult males. In fact, there is no other group of mammals in which female dominance is so widespread. Yet, recent research has indicated that there is more interspecific variation in lemur intersexual relationships than previously acknowledged. Here, we therefore review and summarize the relevant literature, quantifying the extent of sex-bias in intersexual dominance relations documented in observational and experimental studies in captivity and the wild. Female dominance is often, but not always, implemented by spontaneous male submission in the absence of female aggression and linked to female sexual maturation. We connect the available evidence to the hypotheses that have been proposed to explain the evolution of female dominance among lemurs. The occurrence of female dominance in all lemur families and the interspecific variation in its extent indicate that it has evolved soon after lemurs colonized Madagascar – presumably in response to particular ecological challenges – and that it has since been reduced in magnitude independently in some taxa. Our study contributes important comparative information on sex roles from an independent primate radiation and provides general insights into the conditions, opportunities and obstacles in the evolution of female-biased power.
Galleria mellonella Larvae as a Model for Investigating Fungal—Host Interactions
Authors: Curtis Aaron , Binder Ulrike , Kavanagh Kevin
Published: April 2022

Galleria mellonella larvae have become a widely accepted and utilised infection model due to the functional homology displayed between their immune response to infection and that observed in the mammalian innate immune response. Due to these similarities, comparable results to murine studies can be obtained using G. mellonella larvae in assessing the virulence of fungal pathogens and the in vivo toxicity or efficacy of anti-fungal agents. This coupled with their low cost, rapid generation of results, and lack of ethical/legal considerations make this model very attractive for analysis of host-pathogen interactions. The larvae of G. mellonella have successfully been utilised to analyse various fungal virulence factors including toxin and enzyme production in vivo providing in depth analysis of the processes involved in the establishment and progression of fungal pathogens (e.g., Candida spps, Aspergillus spp., Madurella mycetomatis, Mucormycetes, and Cryptococcus neoformans). A variety of experimental endpoints can be employed including analysis of fungal burdens, alterations in haemocyte density or sub-populations, melanisation, and characterisation of infection progression using proteomic, histological or imaging techniques. Proteomic analysis can provide insights into both sides of the host-pathogen interaction with each respective proteome being analysed independently following infection and extraction of haemolymph from the larvae. G. mellonella can also be employed for assessing the efficacy and toxicity of antifungal strategies at concentrations comparable to those used in mammals allowing for early stage investigation of novel compounds and combinations of established therapeutic agents. These numerous applications validate the model for examination of fungal infection and development of therapeutic approaches in vivo in compliance with the need to reduce animal models in biological research.
Identification of SSTR5 Gene Polymorphisms and Their Association With Growth Traits in Hulun Buir Sheep
Authors: Li Xue , Ding Ning , Zhang Zhichao , Tian Dehong , Han Buying , Liu Dehui , Liu Sijia , Tian Fei , Fu Dejun , Song Xiaoliang , Zhao Kai
Published: April 2022

The aim of this study was to locate SSTR5 polymorphisms and evaluate their association with growth traits in Hulun Buir sheep. The study followed up 884 Hulun Buir sheep from birth to 16 months of age, which were born in the same pasture and the same year, and a consistent grazing management strategy was maintained. The birth weight (BRW) was recorded at birth, and body weight (BW), body height (BH), body length (BL), chest circumference (ChC), chest depth (ChD), chest width (ChW), hip width (HW), and cannon circumference (CaC) were measured at 4 and 9 months of age. BW, BH, BL, ChD, HW, and CaC were also recorded at 16 months of age. Based on the growth traits, 233 sheep were selected as experimental animals. Sanger sequencing was performed, and seven single-nucleotide polymorphisms (SNPs) were identified. Association analyses of the SNPs and the growth traits were then conducted. Seven SNPs of the SSTR5 exhibited moderate polymorphism (0.25<PIC<0.5) and were consistent with the Hardy–Weinberg equilibrium. SNP7 (T989C, rs601836309) caused a change in amino acid sequences, while others did not cause any change. The genotypes of SNP1 (C186T, s400914340) were significantly associated with BW, ChW, and ChC at 4 months of age and with HW at 9 months of age (p<0.05). These genotypes also showed extremely significant association with CaC at 4 months of age (p<0.01). The genotypes of SNP7 exhibited a significant association with ChW and CaC at 4 and 9 months of age, respectively. Moreover, the genotypes of SNP3 (T384C, rs413380618)) and SNP4 (T537C, rs605867745) were significantly associated with CaC at 9 months of age (p<0.05). Linkage disequilibrium was observed among the seven SNPs with five haplotypes. However, these haplotypes were not associated with growth traits at different ages. In conclusion, SNP1, SNP3, SNP4, and SNP7 may serve as molecular markers for the growth traits of Hulun Buir sheep.
Case Report: DARS Mutations Responsible for Hypomyelination With Brain Stem and Spinal Cord Involvement and Leg Spasticity
Authors: Liu Meijun , Xiao Wen , Yang Fang , Wang Xueqing , Chen Chao , Jin Shuoguo , Ran Ningjing , Chen Weiyin , Yang Dongdong
Published: April 2022

Objective: Hypomyelination with brain stem and spinal cord involvement and leg spasticity (HBSL) is a rare form of leukodystrophy presenting with varying clinical and imaging features. We report a case of HBSL to investigate the clinical and radiological characteristics of HBSL resulting from cytoplasmic aspartyl-tRNA synthetase gene (DARS) mutations.

Subjects: We report a patient of HBSL with compound heterozygous mutations in DARS1. To study the potential genetic variations of the patient, targeted next-generation sequencing, whole-exome sequencing, and Sanger sequencing were used. We reviewed the clinical and radiological features of the patient. The literature was thoroughly evaluated.

Results: The patient suffered from developmental regression associated with lower limbs spasticity, developmental delay, and paralysis of the lower limbs since childhood. Decreased T1 and increased T2 signals were observed on the bilateral basal, centrum ovale, frontal lobe, parietal lobe, and ganglia in cervical cord magnetic resonance imaging (MRI). The patient had two compound heterozygous mutations (NM_001349:c.1363T > C and NM_001349:c.821C > G) in the DARS1 gene.

Conclusion: Two mutations in DARS1 were found to be associated with HBSL, one of them being reported for the first time. These findings can be valuable for diagnosing and providing genetic counseling to HBSL patients in the future.
Comprehensive Analysis of the Correlation Between Pyroptosis-Related LncRNAs and Tumor Microenvironment, Prognosis, and Immune Infiltration in Hepatocellular Carcinoma
Authors: Qu Guangzhen , Wang Dong , Xu Weiyu , Guo Wei
Published: April 2022

Background: Accumulating evidence shows that pyroptosis plays a crucial role in hepatocellular carcinoma (HCC). However, the relationship between pyroptosis-related long non-coding RNAs (lncRNAs) and HCC tumor characteristics remains enigmatic. We aimed to explore the predictive effect of pyroptosis-related lncRNAs (PRLs) in the prognosis of HCC.

Methods: We comprehensively analyzed the role of the PRLs in the tumor microenvironment and HCC prognosis by integrating genomic data from patients of HCC. Consensus clustering analysis of PRLs was applied to identify HCC subtypes. A prognostic model was then established with a training cohort from The Cancer Genome Atlas (TCGA) using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Further, we evaluated the accuracy of this predictive model using a validation set. We predicted IC50s of commonly used chemotherapeutic and targeted drugs through the R package pRRophetic.

Results: Based on pyroptosis-related lncRNAs, a prognostic risk signature composed of seven PRLs (MKLN1AS, AL031985.3, SNHG4, GHRLOS, AC005479.2, AC099850.4, and AC026412.3) was established. For long-term prognosis of HCC patients, our model shows excellent accuracy to forecast overall survival of HCC individuals both in training set and testing set. We found a significant correlation between clinical features and the risk score. Patients in the high-risk group had tumor characteristics associated with progression such as aggressive pathological grade and stage. Besides that, gene set enrichment analysis (GSEA) showed that cell cycle and focal adhesion were significantly enriched in the high-risk group.

Conclusion: The association of the risk model constituted by these seven pyroptosis-related lncRNAs with clinical prognosis, tumor microenvironment, chemotherapy and small molecule drugs was evaluated. Our study provides strong evidence for individualized prediction of prognosis, shedding light on immunotherapy in HCC patients.
Altered Expressions of NF1 and NF1-Related microRNAs as Biomarkers in the Diagnosis of Undifferentiated Pleomorphic Sarcoma
Authors: Zhang Peng , Huang Lingling , Ma Pengwei , Niu Xiaoying
Published: April 2022

Objective: Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant, aggressive, and pleomorphic subtype of soft tissue sarcoma in adults. However, UPS is difficult to be diagnosed due to the lack of specific morphological and immunophenotypic features. Here, we aimed to identify new biomarkers for the diagnosis of UPS.

Methods: The mRNA and protein expression of neurofibromin 1 (NF1) in 68 pairs of UPS and adjacent normal tissues were detected by qRT-PCR and immunohistochemistry, and the correlation between the NF1 protein expression and clinicopathological characteristics was analyzed. Then, differentially expressed microRNAs (DE miRNAs) were identified between the UPS tumor tissue and matched adjacent normal tissue using Hisep sequencing, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). The DE miRNAs of the regulating NF1 gene were also identified using the TargetScan and miRanda databases and validated by qRT-PCR.

Results: Compared with the adjacent normal tissue, both mRNA and protein expressions of NF1 in the UPS tumor tissue were significantly decreased, and the positive rate of NF1 protein was associated with the tumor size, metastasis, and recurrence. A total of 125 known DE miRNAs were identified from the screened miRNAs based on | log2(Fold Change) ≥5 and p-value < 0.05 (A total of 82 upregulated and 43 downregulated DE miRNAs in the UPS tissue). Target genes regulated by the DE miRNAs were enriched in pathways of metabolisms, RNA degradation, PI3K-Akt, and Rap1 pathway. In total, 11 miRNAs which were predicted to regulate the NF1 gene were screened. After verification, the relative expressions of hsa-miR-199a-3p and hsa-miR-34a-5p were increased and decreased in the UPS tumor tissue compared with those in the adjacent normal tissue, respectively.

Conclusion: NF1 and NF1-related microRNAs including hsa-miR-199a-3p and hsa-miR-34a-5p may be novel biomarkers in the diagnosis of undifferentiated pleomorphic sarcoma (UPS).
Mutations in Growth-Related Genes Induced by EMS Treatment in Scallops
Authors: Wang Caihui , Liu Bo , Chen Min , Ning Junhao , Lu Xia , Wang Chunde
Published: April 2022

Background: The goal of genetic breeding is to select variants with mutations that are related to expected traits, such as fast growth. Artificial induction has been widely used to obtain strains with more mutations for further selection. Ethylmethylsulfone (EMS) is one of the most commonly used chemical mutagens in plant and microorganism breeding. However, the application of EMS mutagenesis in shellfish has not been reported. The aim of this study is to evaluate the potential use of EMS as a mutagen in scallop breeding, especially in characterization of mutations in growth-related genes.

Results: Our results indicated that hatching of about 50% of fertilized eggs was blocked by treatment with 20 mM EMS for 3 h and the resulted larvae developed normally into adult stages. We then evaluated the mutagenic effects of EMS by sequencing the genomes of 4 adult scallops from the control group and 12 from the treatment group at 8 months after fertilization. On average, after removing shared types of mutations, there were 1,151,380 ± 258,188 SNPs (Single Nucleotide Polymorphisms) and 229,256 ± 51,714 InDels (insertion-deletion) in each animal in the EMS treatment group, while there were only134841 ± 10,115 SNPs and 42,605 ± 5,136 InDels in the control group. The average mutation rate in the genome of the EMS treatment group (0.0137 ± 0.0013%) was about 9 times that of the control group (0.0015 ± 0.0002%). GO (Gene Ontology) annotation and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses revealed that mutations induced by EMS occurred evenly in most biological processes, cellular components and functions, as well in most pathways. However, significant lower percentage of mutations were found in the exonic region, in non-synonymous or Stopgain/Stoploss SNPs and in coding domains, suggesting apparent DNA repair or selection during grow-out stage. Analyses of the growth-related genes with mutations indicated that mutations in MFS (Major Facilitator Superfamily) and Tubulin were only found in the large-sized group (Five largest scallops: Treated-1, Treated-2, Treated-3, Treated-4, and Treated-5) and Homeobox and Socs (Suppressor of cytokine signaling) only in the small group (Two smallest scallops: Treated-11 and Treated-12). These results suggested that these genes may be involved in the regulation of growth in these animals, although further verification is certainly warranted.

Conclusion: Treatment of fertilized eggs with 20 mM EMS for 3 h induced 9 times more mutations in scallop genomes. We found that mutations in MFS and Tubulin may be related to fast growth in the large-sized group and those mutations in Homeobox and SOCs may be involved in the slow growth in the small-sized scallops. EMS can be used to accelerate selection of economically important traits in molluscs.
Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes
Authors: Giral Hector , Franke Vedran , Moobed Minoo , Müller Maja F. , Lübking Laura , James Divya Maria , Hartung Johannes , Kuschnerus Kira , Meteva Denitsa , Seppelt Claudio , Jakob Philipp , Klingenberg Roland , Kränkel Nicolle , Leistner David , Zeller Tanja , Blankenberg Stefan , Zimmermann Friederike , Haghikia Arash , Lüscher Thomas F. , Akalin Altuna , Landmesser Ulf , Kratzer Adelheid
Published: April 2022

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release. Both classical and intermediate monocytes from healthy donors exhibited robust CASP1 activation, but only classical monocytes produced high mature interleukin-18 (IL18) release. We also recruited a limited number of coronary artery disease (CAD, n=31) and AMI (n=29) patients to evaluate their inflammasome function and expression profiles. Surprisingly, monocyte subpopulations isolated from blood collected during percutaneous coronary intervention (PCI) from AMI patients presented diminished CASP1 activity and abrogated IL18 release despite increased NLRP3 gene expression. This unexpected attenuated rapid inflammasome activation was accompanied by a significant increase of TNFAIP3 and IRAKM expression. Moreover, TNFAIP3 protein levels of circulating monocytes showed positive correlation with high sensitive troponin T (hsTnT), implying an association between TNFAIP3 upregulation and the severity of tissue injury. We suggest this monocyte attenuation to be a protective phenotype aftermath following a very early inflammatory wave in the ischemic area. Damage-associated molecular patterns (DAMPs) or other signals trigger a transitory negative feedback loop within newly recruited circulating monocytes as a mechanism to reduce post-injury tissue damage.
Competitive Interactions Between Microbial Siderophores and Humic-Like Binding Sites in European Shelf Sea Waters
Authors: Gledhill Martha , Zhu Kechen , Rusiecka Dagmara , Achterberg Eric P.
Published: April 2022

Siderophores are low molecular weight high affinity iron chelates found at low concentrations in seawater. In this study we determined the total concentrations and identities of siderophores in extracts isolated from a shelf sea environment on the Northwest European shelf by high performance liquid chromatography coupled to high resolution inductively coupled plasma mass spectrometry (ICP-MS) in parallel to high resolution electrospray ionisation mass spectrometry (ESI-MS). We identified a total of 24 different siderophores in our samples via metal isotope profiling of masses detected by ESI-MS. Twenty three of the identified siderophores could be assigned to three siderophore families – ferrioxamines, amphibactins and marinobactins. In contrast, only 12 peaks could be resolved in iron chromatograms obtained via ICP-MS analysis. Comparison of results obtained by the two mass spectrometry detectors showed that neither method was able to detect and identify all siderophores present in the samples on its own. We assessed the impact of our observed total siderophore concentrations on iron speciation by calculating the distribution of iron species as a function of total siderophore concentrations at different iron concentrations representative of our study area. We considered competition for iron between siderophores, a humic like dissolved organic matter (DOM) fraction and hydroxide ions by combining an ion-pair model with a non-ideal competitive interaction (NICA)-Donnan model. We found that the overall impact of siderophores on iron biogeochemistry is low at concentrations of siderophore <100 pmol L-1, and that the dominant iron species present at siderophore concentrations of the order of a few tens of pmol L-1 will be iron bound to the humic like DOM fraction. Furthermore the heterogeneity of binding sites in the humic like DOM fraction means that other binding sites present in organic matter could be effective competitors for siderophores, especially at low iron concentrations. Our findings highlight the importance of binding site heterogeneity when considering the influence of different iron binding groups on iron speciation in the marine environment.
Cell Factory Engineering of Undomesticated Bacillus Strains Using a Modified Integrative and Conjugative Element for Efficient Plasmid Delivery
Authors: Jeong Da-Eun , Kim Man Su , Kim Ha-Rim , Choi Soo-Keun
Published: April 2022

A large number of Bacillus strains have been isolated from various environments and many of them have great potential as cell factories. However, they have been rarely developed as cell factories due to their poor transformation efficiency. In this study, we developed a highly efficient plasmid delivery system for undomesticated Bacillus strains using a modified integrative and conjugative element (MICE), which was designed to be activated by an inducer, prevent self-transfer, and deliver desired plasmids to the recipient cells. The MICE system was demonstrated to successfully introduce a gfp-containing plasmid into all 41 undomesticated Bacillus subtilis strains tested and eight other Bacillus species. The MICE was used to deliver a cytosine base editor (CBE)-based multiplex genome-editing tool for the cell factory engineering of the Bacillus species. The introduced CBE enabled one-step inactivation of the major extracellular protease genes of the tested strains. The engineered strains were used as hosts for heterologous expression of nattokinase, which resulted in various enzyme expression levels. The results suggested that the MICE and CBE systems can be powerful tools for genetic engineering of undomesticated Bacillus strains, and greatly contribute to the expansion of the Bacillus cell factory.
HIV-1-Transmitted Drug Resistance and Transmission Clusters in Newly Diagnosed Patients in Portugal Between 2014 and 2019
Authors: Pingarilho Marta , Pimentel Victor , Miranda Mafalda N. S. , Silva Ana Rita , Diniz António , Ascenção Bianca Branco , Piñeiro Carmela , Koch Carmo , Rodrigues Catarina , Caldas Cátia , Morais Célia , Faria Domitília , da Silva Elisabete Gomes , Teófilo Eugénio , Monteiro Fátima , Roxo Fausto , Maltez Fernando , Rodrigues Fernando , Gaião Guilhermina , Ramos Helena , Costa Inês , Germano Isabel , Simões Joana , Oliveira Joaquim , Ferreira José , Poças José , da Cunha José Saraiva , Soares Jorge , Henriques Júlia , Mansinho Kamal , Pedro Liliana , Aleixo Maria João , Gonçalves Maria João , Manata Maria José , Mouro Margarida , Serrado Margarida , Caixeiro Micaela , Marques Nuno , Costa Olga , Pacheco Patrícia , Proença Paula , Rodrigues Paulo , Pinho Raquel , Tavares Raquel , de Abreu Ricardo Correia , Côrte-Real Rita , Serrão Rosário , Castro Rui Sarmento e , Nunes Sofia , Faria Telo , Baptista Teresa , Martins Maria Rosário O. , Gomes Perpétua , Mendão Luís , Simões Daniel , Abecasis Ana
Published: April 2022

Objective

To describe and analyze transmitted drug resistance (TDR) between 2014 and 2019 in newly infected patients with HIV-1 in Portugal and to characterize its transmission networks.

Methods

Clinical, socioepidemiological, and risk behavior data were collected from 820 newly diagnosed patients in Portugal between September 2014 and December 2019. The sequences obtained from drug resistance testing were used for subtyping, TDR determination, and transmission cluster (TC) analyses.

Results

In Portugal, the overall prevalence of TDR between 2014 and 2019 was 11.0%. TDR presented a decreasing trend from 16.7% in 2014 to 9.2% in 2016 (pfor–trend = 0.114). Multivariate analysis indicated that TDR was significantly associated with transmission route (MSM presented a lower probability of presenting TDR when compared to heterosexual contact) and with subtype (subtype C presented significantly more TDR when compared to subtype B). TC analysis corroborated that the heterosexual risk group presented a higher proportion of TDR in TCs when compared to MSMs. Among subtype A1, TDR reached 16.6% in heterosexuals, followed by 14.2% in patients infected with subtype B and 9.4% in patients infected with subtype G.

Conclusion

Our molecular epidemiology approach indicates that the HIV-1 epidemic in Portugal is changing among risk group populations, with heterosexuals showing increasing levels of HIV-1 transmission and TDR. Prevention measures for this subpopulation should be reinforced.