bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Angular Deformity Due to Sacrococcygeal Fracture Cause Permanent Impairment? : Current State and Problems in Korea
Authors: Cho Dosang
Published: December 2021

Disabilities can emerge due to traumatic spinal fractures. In terms of sacrococcygeal spine, because of its unique anatomic structure with minimal movement, the possibility for it to have a disability is relatively low. In Korea, unlike most disability criteria, private insurance companies acknowledge angular deformities caused by vertebral fractures as disabilities according to their degree, so there were several cases where patients required compensation, arguing angular deformity caused by sacrococcygeal fracture, which in some cases led to legal conflicts. Except the Act Welfare of Persons with Disabilities which recognizes only severe angular deformity affecting internal organs as disability and the industrial accident disability evaluation which does not recognize coccygeal fracture as disability but rarely recognizes sacral vertebra deformity equivalent to compressive deformation, there is little or no case where angular deformity is recognized as disability. Given the impairment evaluation standards in social insurance, McBride system, American Medical Association (AMA) guides, and newly proposed standards by the Korean Academy of Medical Sciences (KAMS), the most contentious point in the general terms and conditions of private insurance is spinal deformity. To overcome controversy over disability evaluation, the private insurance sector is now applying criteria for axial skeleton to sacrococcygeal vertebrae through revision of standards. Under these circumstances, it is fair to recognize sacrococcygeal fracture as impairment in terms of the pelvis only when the fracture leaves serious deformity and neurological symptoms with clear relevancy. Though it may not be easy to develop accurate disability evaluation standards, improvement is necessary to remove any irrationalities and make the standards as objective as possible.
Epidemiological characterization and spatial distribution of visceral leishmaniasis cases in Três Lagoas - MS, Brazil in the period of 2007-2021
Authors: Carvalho Giovanna Bruna de Almeida , Caldeira João Victor Camargo , Oliveira Mirian Daiane de , Oda Juliano Yasuo , Machado Alex Martins , Machado Aline Rafaela da Silva Rodrigues
Published: December 2021

This retrospective observational cross-sectional study aimed to analyze the distribution of visceral leishmaniasis (VL) cases in Três Lagoas registered between January 2007 and August 2021, through data processed by the Epidemiological Surveillance Service based on the notification of the National System of Diseases and Notifications. In this period, 231 cases were confirmed, being 137 male (59.3%) and 94 female (40.7%). Was observed a higher prevalence of cases between ages 0-4 years (30.8%), 20-39 (22.5%) and 40-59 (19.9%). Also was observed a higher percentage of infected Caucasian individuals (45.4%) and individuals with low education: elementary school II (22.1%). The most prevalent clinical manifestations were fever (85.3%), splenomegaly (76.6%), weakness (67.1%), weight loss (65.8%) and hepatomegaly (62.8%). It was found that 80.1% of patients received pharmacological treatment, mainly using pentavalent antimonials (56.7%), and that 26 patients (11.3%) died during the period due to complications caused by VL. The spatial analysis showed a homogeneous distribution of VL cases in the city's urban perimeter without predominant regions. Finally, it was observed that the incidence and mortality by VL has been decreasing in recent years, however maintaining high rates of lethality and transmissibility, placing the municipality in the third with the highest transmission rate in the state. In view of these aspects, we conclude that VL is still a serious public health problem in the city and that despite the slight drop in incidence and mortality rates, it still presents values higher than the national average and high dissemination of the disease in the urban area.
A new perspective on cholesterol in pediatric health: association of vitamin D metabolism, respiratory diseases, and mental health problems
Authors: Hong Jeana
Published: December 2021

Cholesterol, the main structural molecule of cell membranes, is involved in essential functions of the human body. Dyslipidemia is an established risk factor for cardiovascular diseases (CVDs) that is observed even in childhood. To reduce the risk of CVDs in children, several clinical guidelines have been published for the management of pediatric dyslipidemia. However, pediatric dyslipidemia is also associated with several health problems other than CVDs. This article reviews the current data on dyslipidemia-related pediatric health issues. There is strong evidence that low serum vitamin D levels, asthma, and mental health problems may be associated with dyslipidemia in the pediatric population regardless of body mass index. This review also highlights the need for further large-scale population-based studies in the Korean pediatric population to establish effective strategies for promoting children’s health.
Endothelial-Mesenchymal Transition or Functional Tissue Regeneration – Two Outcomes of Heart Remodeling
Authors: Šalingová B. , Červenák Z. , Adamičková A. , Chomanicová N. , Valášková S. , Gažová A. , Kyselovič J.
Published: December 2021

Heart remodeling occurs as a compensation mechanism for the massive loss of tissue during initial heart failure and the consequent inflammation process. During heart remodeling fibroblasts differentiate to myofibroblasts activate their secretion functions and produce elevated amounts, of extracellular matrix (ECM) proteins, mostly collagen, that form scar tissue and alter the normal degradation of ECM. Scar formation does replace the damaged tissue structurally; however, it impedes the normal contractive function of cardiomyocytes (CMs) and results in long-lasting effects after heart failure. Besides CMs and cardiac fibroblasts, endothelial cells (ECs) and circulating endothelial progenitor cells (cEPCs) contribute to heart repair. This review summarizes the current knowledge of EC-CM crosstalk in cardiac fibrosis (CF), the role of cEPCs in heart regeneration and the contribution of Endothelial-mesenchymal transition (EndoMT).
A Case Series of Eight Coronary Artery Perforations and a Review of the Up-to-Date Literature
Authors: James Sunil , Hunter George
Published: December 2021

Percutaneous coronary intervention has become a fundamental diagnostic and treatment strategy in coronary artery disease. Much like any procedure, it is not without risk; in fact, a rare but life-threatening complication as a result of percutaneous coronary intervention is coronary artery perforations (CAP). The risk of CAPs correspondingly rises in relation to the difficulty of the procedure, location of lesion, and complexity of anatomy. It follows then that early recognition and instigation of an appropriate treatment strategy is key in reducing the mortality and morbidity associated with CAPs. The authors present eight case reports of varying difficulties, their analogous management, and a literature review of management approaches in treating CAPs in order to provide a review of management strategies and to highlight the importance of immediate recognition of a potentially fatal complication.
2021 ESC Guidelines for the Diagnosis and Treatment of Acute and
Chronic Heart Failure
Authors: Meunier-McVey Natasha
Published: December 2021

An engaging session on the newly revised European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) was conducted on the first day of the 2021 ESC virtual congress. Chaired by Colin Baigent, Professor of Epidemiology, University of Oxford, UK, the session also explored the classification and management of HF, and addressed questions from the congress audience.
Excesso? O debate sobre o nível das reservas internacionais no Brasil
Authors: Rodrigues de Oliveira Cinthia , Leonardo de Araujo Victor
Published: December 2021

Desde o final dos anos 1990, os países periféricos passaram a acumular reservas internacionais em resposta às sucessivas crises cambiais deste período. Desde então, manter estoques de reservas tornou-se uma estratégia de gestão da política cambial destas economias, sobretudo, a partir da crise financeira global de 2008, quando ocorreu um aumento de forma acelerada dos ativos externos nos países periféricos possibilitado pela melhora dos termos de trocas e das baixas taxas de juros internacionais. No Brasil, as reservas internacionais passaram de US$ 36,3 bilhões em 1999, para US$ 206,8 bilhões em 2008 e US$ 345,7 bilhões em 2020. Contudo, o acúmulo de reservas internacionais tem como contrapartida a geração de custos associados à sua manutenção, ensejando o debate a respeito de um nível ótimo de reservas para o Brasil. Mais recentemente, a deterioração dos indicadores fiscais no Brasil motivou um debate sobre usos alternativos para o excesso de reservas, tendo se destacado as propostas de utilizá-lo no abatimento da dívida pública ou para o financiamento do investimento público. Este artigo pretende contribuir para estedebate, defendendo que o nível integral das reservas internacionais seja preservado.
The Price of Surviving on Adrenaline: Developmental Programming Responses to Chronic Fetal Hypercatecholaminemia Contribute to Poor Muscle Growth Capacity and Metabolic Dysfunction in IUGR-Born Offspring
Authors: Gibbs Rachel L. , Yates Dustin T.
Published: December 2021

Maternofetal stress induces fetal programming that restricts skeletal muscle growth capacity and metabolic function, resulting in intrauterine growth restriction (IUGR) of the fetus. This thrifty phenotype aids fetal survival but also yields reduced muscle mass and metabolic dysfunction after birth. Consequently, IUGR-born individuals are at greater lifelong risk for metabolic disorders that reduce quality of life. In livestock, IUGR-born animals exhibit poor growth efficiency and body composition, making these animals more costly and less valuable. Specifically, IUGR-associated programming causes a greater propensity for fat deposition and a reduced capacity for muscle accretion. This, combined with metabolic inefficiency, means that these animals produce less lean meat from greater feed input, require more time on feed to reach market weight, and produce carcasses that are of less quality. Despite the health and economic implications of IUGR pathologies in humans and food animals, knowledge regarding their specific underlying mechanisms is lacking. However, recent data indicate that adaptive programing of adrenergic sensitivity in multiple tissues is a contributing factor in a number of IUGR pathologies including reduced muscle mass, peripheral insulin resistance, and impaired glucose metabolism. This review highlights the findings that support the role for adrenergic programming and how it relates to the lifelong consequences of IUGR, as well as how dysfunctional adrenergic signaling pathways might be effective targets for improving outcomes in IUGR-born offspring.
FSTL1-USP10-Notch1 Signaling Axis Protects Against Cardiac Dysfunction Through Inhibition of Myocardial Fibrosis in Diabetic Mice
Authors: Lu Linhe , Ma Jipeng , Liu Yang , Shao Yalan , Xiong Xiang , Duan Weixun , Gao Erhe , Yang Qianli , Chen Shasha , Yang Jian , Ren Jun , Zheng Qijun , Liu Jincheng
Published: December 2021

The incidence of type 2 diabetes mellitus (T2DM) has been increasing globally, and T2DM patients are at an increased risk of major cardiac events such as myocardial infarction (MI). Nevertheless, the molecular mechanisms underlying MI injury in T2DM remain elusive. Ubiquitin-specific protease 10 (USP10) functions as a NICD1 (Notch1 receptor) deubiquitinase that fine-tunes the essential myocardial fibrosis regulator Notch signaling. Follistatin-like protein 1 (FSTL1) is a cardiokine with proven benefits in multiple pathological processes including cardiac fibrosis and insulin resistance. This study was designed to examine the roles of FSTL1/USP10/Notch1 signaling in MI-induced cardiac dysfunction in T2DM. High-fat-diet-treated, 8-week-old C57BL/6J mice and db/db T2DM mice were used. Intracardiac delivery of AAV9-FSTL1 was performed in T2DM mice following MI surgery with or without intraperitoneal injection of crenigacestat (LY3039478) and spautin-1. Our results demonstrated that FSTL1 improved cardiac function following MI under T2DM by reducing serum lactate dehydrogenase (LDH) and myocardial apoptosis as well as cardiac fibrosis. Further in vivo studies revealed that the protective role of FSTL1 against MI injury in T2DM was mediated by the activation of USP10/Notch1. FSTL1 protected cardiac fibroblasts (CFs) against DM-MI-induced cardiofibroblasts injury by suppressing the levels of fibrosis markers, and reducing LDH and MDA concentrations in a USP10/Notch1-dependent manner. In conclusion, FSTL1 treatment ameliorated cardiac dysfunction in MI with co-existent T2DM, possibly through inhibition of myocardial fibrosis and apoptosis by upregulating USP10/Notch1 signaling. This finding suggests the clinical relevance and therapeutic potential of FSTL1 in T2DM-associated MI and other cardiovascular diseases.
Integral Analyses of Competing Endogenous RNA Mechanisms and DNA Methylation Reveal Regulatory Mechanisms in Osteosarcoma
Authors: Wu Tingrui , Wei Bo , Lin Hao , Zhou Boan , Lin Tao , Liu Qianzheng , Sang Hongxun , Liu Huan , Huang Wenhua
Published: December 2021

Background: Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents, with rapid growth, frequent metastasis, and a poor prognosis, but its pathogenesis has not been fully elucidated. Exploring the pathogenesis of OS is of great significance for improving diagnoses and finding new therapeutic targets.

Methods: Differentially expressed circRNAs (DECs), miRNAs (DEMs), methylated DNA sites (DMSs), and mRNAs (DEGs) were identified between OS and control cell lines. GSEA of DEGs and functional enrichment analysis of methylated DEGs were carried out to further identify potential biological processes. Online tools were used to predict the miRNA binding sites of DECs and the mRNA binding sites of DEMs, and then construct a circRNA-miRNA-mRNA network. Next, an analysis of the interaction between methylated DEGs was performed with a protein-protein interaction (PPI) network, and hub gene identification and survival analysis were carried out. The expression pattern of circRNA-miRNA-mRNA was validated by real-time PCR.

Results: GSEA and functional enrichment analysis indicated that DEGs and methylated DEGs are involved in important biological processes in cancer. Hsa_circ_0001753/has_miR_760/CD74 network was constructed and validated in cell lines. Low expression levels of CD74 are associated with poor overall survival times and show good diagnostic ability.

Conclusion: Methylated DEGs may be involved in the development of OS, and the hsa_circ_0001753/has_miR_760/CD74 network may serve as a target for the early diagnosis of and targeted therapy for OS.
Targeted Methylation of the LncRNA NEAT1 Suppresses Malignancy of Renal Cell Carcinoma
Authors: Chen Jieqing , Liao Xinhui , Cheng Jianli , Su Ganglin , Yuan Fen , Zhang Zhongfu , Wu Jianting , Mei Hongbing , Tan Wanlong
Published: December 2021

Long-chain non-coding RNA (LncRNA) has been found to play an important role in the regulation of the occurrence and progression of renal cell carcinoma (RCC). In this study, we demonstrated that LncRNA NEAT1 expression and m6A methylation level was decreased in RCC tissues. Further, the downregulated expression level of LncRNA NEAT1 was associated with poor prognosis for RCC patients. Then we used CRIPSR/dCas13b-METTL3 to methylate LncRNA NEAT1 in RCC cells. The results showed that the expression level of LncRNA NEAT1 was upregulated after methylated by dCas13b-METTL3 in RCC cells. And the proliferation and migration ability of RCC cells was decreased after methylated LncRNA NEAT1. Finally, we examined the effect of LncRNA NEAT1 hypermethylation on the transcriptome. We found differentially expressed genes in RCC cells were associated with “cGMP-PKG signaling pathway”, “Cell adhesion molecules” and “Pathways in cancer”. In conclusion, CRISPR/Cas13b-METTL3 targeting LncRNA NEAT1 m6A methylation activates LncRNA NEAT1 expression and provides a new target for treatment of RCC.
Triterpenoids From Kadsura coccinea With Their Anti-inflammatory and Inhibited Proliferation of Rheumatoid Arthritis-Fibroblastoid Synovial Cells Activities
Authors: Yang Yu-pei , Jian Yu-qing , Liu Yong-bei , Ismail Muhammad , Xie Qing-ling , Yu Huang-he , Wang Bin , Li Bin , Peng Cai-yun , Liu Bin , Man Rong-yong , Wang Wei
Published: December 2021

One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3–4) and heilaohumethylesters A-C (7–9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10–31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, 13C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC50 values of 8.15 and 9.86 μM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC50 values of 7.52, 8.85, and 7.97 μM, respectively.
Gastrointestinal Microbiota Changes in Patients With Gastric Precancerous Lesions
Authors: Liu Dehua , Chen Si , Gou Yawen , Yu Wenyong , Zhou Hangcheng , Zhang Rutong , Wang Jinghao , Ye Fei , Liu Yingling , Sun Baolin , Zhang Kaiguang
Published: December 2021

Background

Gastric microbiota may be involved in gastric cancer. The relationship between gastrointestinal microbes and the risk of gastric cancer is unclear. This study aimed to explore the gastric and intestinal bacteria associated with gastritis and gastric precancerous lesions. We conducted a case-control study by performing 16S rRNA gene analysis of gastric biopsies, juices, and stool samples from 148 cases with gastritis or gastric precancerous lesions from Anhui and neighboring provinces, China. And we validated our findings in public datasets.

Results

Analysis of microbial sequences revealed decreased bacterial alpha diversity in gastric bacteria during the progression of gastritis. Helicobacter pylori was the main contributor to the decreased microbial composition and diversity in the gastric mucosa and had little influence on the microbiota of gastric juice and feces. The gastric mucosal genera Gemella, Veillonella, Streptococcus, Actinobacillus, and Hemophilus had the higher degree of centrality across the progression of gastric precancerous lesions. And Acinetobacter may contribute to the occurrence of intraepithelial neoplasia. In addition, the microbial model of H. pylori-positive gastric biopsies and feces showed value in the prediction of gastric precancerous lesions.

Conclusions

This study identified associations between gastric precancerous lesions and gastric microbiota, as well as the changes in intestinal microbiota, and explored their values in the prediction of gastric precancerous lesions.
SynActJ: Easy-to-Use Automated Analysis of Synaptic Activity
Authors: Schmied Christopher , Soykan Tolga , Bolz Svenja , Haucke Volker , Lehmann Martin
Published: December 2021

Neuronal synapses are highly dynamic communication hubs that mediate chemical neurotransmission via the exocytic fusion and subsequent endocytic recycling of neurotransmitter-containing synaptic vesicles (SVs). Functional imaging tools allow for the direct visualization of synaptic activity by detecting action potentials, pre- or postsynaptic calcium influx, SV exo- and endocytosis, and glutamate release. Fluorescent organic dyes or synapse-targeted genetic molecular reporters, such as calcium, voltage or neurotransmitter sensors and synapto-pHluorins reveal synaptic activity by undergoing rapid changes in their fluorescence intensity upon neuronal activity on timescales of milliseconds to seconds, which typically are recorded by fast and sensitive widefield live cell microscopy. The analysis of the resulting time-lapse movies in the past has been performed by either manually picking individual structures, custom scripts that have not been made widely available to the scientific community, or advanced software toolboxes that are complicated to use. For the precise, unbiased and reproducible measurement of synaptic activity, it is key that the research community has access to bio-image analysis tools that are easy-to-apply and allow the automated detection of fluorescent intensity changes in active synapses. Here we present SynActJ (Synaptic Activity in ImageJ), an easy-to-use fully open-source workflow that enables automated image and data analysis of synaptic activity. The workflow consists of a Fiji plugin performing the automated image analysis of active synapses in time-lapse movies via an interactive seeded watershed segmentation that can be easily adjusted and applied to a dataset in batch mode. The extracted intensity traces of each synaptic bouton are automatically processed, analyzed, and plotted using an R Shiny workflow. We validate the workflow on time-lapse images of stimulated synapses expressing the SV exo-/endocytosis reporter Synaptophysin-pHluorin or a synapse-targeted calcium sensor, Synaptophysin-RGECO. We compare the automatic workflow to manual analysis and compute calcium-influx and SV exo-/endocytosis kinetics and other parameters for synaptic vesicle recycling under different conditions. We predict SynActJ to become an important tool for the analysis of synaptic activity and synapse properties.
Relationship Between Sarcopenia and Cardiovascular Diseases in the Elderly: An Overview
Authors: He Nana , Zhang Yuelin , Zhang Lu , Zhang Shun , Ye Honghua
Published: December 2021

With the advent of population aging, aging-related diseases have become a challenge for governments worldwide. Sarcopenia has defined as a clinical syndrome associated with age-related loss such as skeletal muscle mass, strength, function, and physical performance. It is commonly seen in elderly patients with chronic diseases. Changes in lean mass are common critical determinants in the pathophysiology and progression of cardiovascular diseases (CVDs). Sarcopenia may be one of the most important causes of poor physical function and decreased cardiopulmonary function in elderly patients with CVDs. Sarcopenia may induce CVDs through common pathogenic pathways such as malnutrition, physical inactivity, insulin resistance, inflammation; these mechanisms interact. In this study, we aimed to investigate the relationship between sarcopenia and CVDs in the elderly. Further research is urgently needed to understand better the relationship, pathophysiology, clinical presentation, diagnostic criteria, and mechanisms of sarcopenia and CVDs, which may shed light on potential interventions to improve clinical outcomes and provide greater insight into the disorders above.
Prognostic Value of Multiple Circulating Biomarkers for 2-Year Death in Acute Heart Failure With Preserved Ejection Fraction
Authors: Gao Yan , Bai Xueke , Lu Jiapeng , Zhang Lihua , Yan Xiaofang , Huang Xinghe , Dai Hao , Wang Yanping , Hou Libo , Wang Siming , Tian Aoxi , Li Jing
Published: December 2021

Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a major global public health burden and lacks effective risk stratification. We aimed to assess a multi-biomarker model in improving risk prediction in HFpEF.

Methods: We analyzed 18 biomarkers from the main pathophysiological domains of HF in 380 patients hospitalized for HFpEF from a prospective cohort. The association between these biomarkers and 2-year risk of all-cause death was assessed by Cox proportional hazards model. Support vector machine (SVM), a supervised machine learning method, was used to develop a prediction model of 2-year all-cause and cardiovascular death using a combination of 18 biomarkers and clinical indicators. The improvement of this model was evaluated by c-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

Results: The median age of patients was 71-years, and 50.5% were female. Multiple biomarkers independently predicted the 2-year risk of death in Cox regression model, including N-terminal pro B-type brain-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), growth differentiation factor-15 (GDF-15), tumor necrosis factor-α (TNFα), endoglin, and 3 biomarkers of extracellular matrix turnover [tissue inhibitor of metalloproteinases (TIMP)-1, matrix metalloproteinase (MMP)-2, and MMP-9) (FDR < 0.05). The SVM model effectively predicted the 2-year risk of all-cause death in patients with acute HFpEF in training set (AUC 0.834, 95% CI: 0.771–0.895) and validation set (AUC 0.798, 95% CI: 0.719–0.877). The NRI and IDI indicated that the SVM model significantly improved patient classification compared to the reference model in both sets (p < 0.05).

Conclusions: Multiple circulating biomarkers coupled with an appropriate machine-learning method could effectively predict the risk of long-term mortality in patients with acute HFpEF. It is a promising strategy for improving risk stratification in HFpEF.
Evaluating the Role of Breathing Guidance on Game-Based Interventions for Relaxation Training
Authors: Gummidela Venkata Nitin Chakravarthy , Silva Dennis R. da Cunha , Gutierrez-Osuna Ricardo
Published: December 2021

Working in a fast-paced environment can lead to shallow breathing, which can exacerbate stress and anxiety. To address this issue, this study aimed to develop micro-interventions that can promote deep breathing in the presence of stressors. First, we examined two types of breathing guides to help individuals learn deep breathing: providing their breathing rate as a biofeedback signal, and providing a pacing signal to which they can synchronize their breathing. Second, we examined the extent to which these two breathing guides can be integrated into a casual game, to increase enjoyment and skill transfer. We used a 2 × 2 factorial design, with breathing guide (biofeedback vs. pacing) and gaming (game vs. no game) as independent factors. This led to four experimental groups: biofeedback alone, biofeedback integrated into a game, pacing alone, and pacing integrated into a game. In a first experiment, we evaluated the four experimental treatments in a laboratory setting, where 30 healthy participants completed a stressful task before and after performing one of the four treatments (or a control condition) while wearing a chest strap that measured their breathing rate. Two-way ANOVA of breathing rates, with treatment (5 groups) and time (pre-test, post-test) as independent factors shows a significant effect for time [F(4, 50) = 18.49, p < 0.001, ηtime2=0.27] and treatment [F(4, 50) = 2.54, p = 0.05, η2 = 0.17], but no interaction effects. Post-hoc t-tests between pre and post-test breathing rates shows statistical significance for the game with biofeedback group [t(5) = 5.94, p = 0.001, d = 2.68], but not for the other four groups, indicating that only game with biofeedback led to skill transfer at post-test. Further, two-way ANOVA of self-reported enjoyment scores on the four experimental treatments, with breathing guide and game as independent factors, found a main effect for game [F(1,20)=24.49,p<0.001, ηgame2=0.55], indicating that the game-based interventions were more enjoyable than the non-game interventions. In a second experiment, conducted in an ambulatory setting, 36 healthy participants practiced one of the four experimental treatments as they saw fit over the course of a day. We found that the game-based interventions were practiced more often than the non-game interventions [t (34) = 1.99, p = 0.027, d = 0.67]. However, we also found that participants in the game-based interventions could only achieve deep breathing 50% of the times, whereas participants in the non-game groups succeeded 85% of the times, which indicated that the former need adequate training time to be effective. Finally, participant feedback indicated that the non-game interventions were better at promoting in-the-moment relaxation, whereas the game-based interventions were more successful at promoting deep breathing during stressful tasks.
The Thermal and Settlement Characteristics of Crushed-Rock Structure Embankments of the Qinghai-Tibet Railway in Permafrost Regions Under Climate Warming
Authors: Mei Qihang , Yang Bin , Chen Ji , Zhao Jingyi , Hou Xin , Liu Youqian , Wang Jinchang , Zhang Shouhong , Dang Haiming
Published: December 2021

The temperature difference at the top and bottom of the crushed-rock layer can drive the heat convection inside. Based on this mechanism, crushed-rock structures with different forms are widely used in the construction and maintenance of the Qinghai-Tibet Railway as cooling measures in permafrost regions. To explore the stability of different forms of crushed-rock structure embankments under climate warming, the temperature and deformation data of a U-shaped crushed-rock embankment (UCRE) and a crushed-rock revetment embankment (CRRE) are analysed. The variations in temperature indicate that permafrost beneath the natural sites and embankments is degrading but at different rates. The thermal regime of ground under the natural site is only affected by climate warming, while that under embankment is also affected by embankment construction and the cooling effect of the crushed-rock structure. These factors make shallow permafrost degradation beneath the embankments slower than that beneath the natural sites and deep permafrost degradation faster than that beneath the natural sites. Moreover, the convection occurring in the crushed-rock base layer during the cold season makes the degradation of permafrost beneath the UCRE slower than that in the CRRE. The faster degradation of permafrost causes the accumulated deformation of the CRRE to be far greater than that of the UCRE, which may exceed the allowable value of the design code. The analysis shows that the stability of the UCRE meets the engineering requirements and the CRRE needs to be strengthened in warm and ice-rich permafrost regions under climate warming.
Understanding Wealth Inequalities in Education Access in Urbanizing Sub-Saharan Africa
Authors: Mutisya Maurice , Muchira John Munyui , Abuya Benta A.
Published: December 2021

Introduction: Urbanization is a double-edged sword, while it is transforming the world, it is also creating spaces that pose threats to its benefits. In sub-Saharan Africa, urbanization is occurring amidst slowed economic growth and into spaces that are already strained. This is resulting in the growth of urban poverty and possibly increasing inequalities. It is thus imperative to understand the effects of urbanization in realizing inclusive and equitable education for all.

Objective: We examine inequalities in enrolment of schooling going children aged 6–17 years living in urban areas using the latest Demographic and Health Surveys data from 24 SSA countries.

Methods: We utilize three measures of inequality: Rate difference, rate ratio, and relative concentration index to examine inequalities in education access. Using wealth status as the key inequality indicator, we compute and compare school enrollment of children living in urban poor households with that of those living in urban rich households for each measure of inequality. Where appropriate, we stratify the results by country, age, and gender.

Results: The results show high levels of inequalities in education access in urban settings. Across all the measures of inequality, in most countries, children from urban poor households were significantly less likely to be in school compared to those from the richest ranked households. The degree of inequality varied considerably between countries and the age groups. Among children aged 6–11 years, Tanzania, Burundi, Nigeria, and Uganda had the highest degree of inequality favouring the urban rich. We also find intriguing results in few countries such as Ethiopia, Benin, Senegal and Mali, which the urban poor had, better school enrolments than the urban rich. We do not find a clear pattern to suggest girls from poor households are overly disadvantaged than boys from similar households.

Conclusion: Our study shows a high level of inequalities in education access in an urban setting, with children age in urban poor settings hugely disadvantaged. There is a need for strategic efforts in terms of deliberate interventions and policy frameworks to combat the apparent inequalities that disadvantage children from poor families from accessing education.
The Impact of Entrepreneurship Perceptions on Entrepreneurial Intention During the COVID-19 Pandemic
Authors: Li Pei , Li Bing , Liu Ziyang
Published: December 2021

The global pandemic of COVID-19 is a challenge for entrepreneurship education in universities and various organizations. Although positive responses to overcome the challenges of COVID-19 are being made, entrepreneurship strategies and policies might not meet students’ requirements. In order to enrich education management research, the main aim of this study is to provide a conceptual model and examine the relationship between perceptions, perceived positive attitudes on entrepreneurship education, and entrepreneurial intention (EI) during the COVID-19 crisis. The model is tested by using data from universities that are located in Shanghai, P.R. China. The study reveals that 1) perceived social norms and perceived self-efficacy positively influence perceived positive attitudes in entrepreneurship education; 2) there is no relationship between perceived entrepreneurial barriers and perceived positive attitudes in entrepreneurship education; 3) perceived positive attitudes in entrepreneurship education positively influence EI. The findings contribute to university and government policies on the development of entrepreneurial education. The framework of this study provides insight into the influential factors of entrepreneurship education that contribute to theoretical studies in the COVID-19 pandemic.
The Impact of Promoting Alternative Thinking Strategies (PATHS) on Loneliness in Primary School Children: Results From a Randomized Controlled Trial in England
Authors: Hennessey Alexandra , Qualter Pamela , Humphrey Neil
Published: December 2021

Research suggests that loneliness during childhood is associated with poor well-being and mental ill-health. There is a growing social and educational imperative to explore how school-based interventions can support young children’s social development. The Promoting Alternative Thinking Strategies (PATHS) curriculum is a universal school intervention focused on social and emotional learning, and it has a significant evidence based supporting its positive impact on children’s social-emotional and mental health outcomes. Yet the impact on children’s reported loneliness has not been explored. This paper presents the first large scale analyses of the impact of PATHS on reducing children’s loneliness in England. A cluster randomized controlled trial (RCT) with two arms: intervention (PATHS—23 schools) and control (usual practice—22 schools) assessed the impact of PATHS on children’s loneliness from baseline to 2-year follow-up. Two-level (school, child) multi-nomial regression models were used to assess “intention-to-treat” effects, controlling for important demographic co-variates such as gender, age, free school meal eligibility, ethnicity, and special educational needs. These analyses revealed a significant positive effect of PATHS on children’s loneliness. Furthermore, sensitivity analyses, treating loneliness as a dichotomous variable and using different cut-offs for loneliness, revealed the positive effect of PATHS was maintained and, thus, robust. This is the first RCT to demonstrate that a school-based universal social-emotional learning intervention such as PATHS can reduce loneliness in children.
Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth
Authors: Huang Jia-Shuan , Chen Qiao-Zhu , Zheng Si-Yu , Ramakrishnan Rema , Zeng Ji-Yuan , Zhuo Can-Peng , Lai Yu-Mian , Kuang Ya-Shu , Lu Jin-Hua , He Jian-Rong , Qiu Xiu
Published: December 2021

Background

Birth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors.

Methods

We included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22–27, 28–36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors.

Results

Fetal weight at each period was positively associated with insulin levels, with stronger association at 28–36 weeks (β, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (β, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28–36 (β, −0.32; 95% CI, −0.39 to −0.24) and ≥37 weeks (β, −0.26; 95% CI, −0.31 to −0.21) was negatively associated with triglyceride levels, whereas weight at 28–36 weeks was positively associated with HDL levels (β, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22–27 weeks was associated with increased levels of insulin, glucose, and HDL.

Conclusions

Fetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.
Gradual, but Not Sudden, Dose-Dependent Increase of ONJ Risk With Bisphosphonate Exposure: A Nationwide Cohort Study in Women With Osteoporosis
Authors: Park Jung-Hyun , Kwoen Min-Jeong , Lee Jae-Ryun , Kim Keun-Suh , Lee Hyo-Jung , Kim Jin-Woo , Lee Hyejin
Published: December 2021

Background

A causal relationship of bisphosphonate (BP) exposure with osteonecrosis of the jaw (ONJ) has been reported; however, a definite dose-dependent risk remains to be elucidated beyond current vague recommendations of 4-year oral BP for ONJ risk increase.

Objective

To identify the effect of bisphosphonate cumulative dose on ONJ development in women with osteoporosis.

Methods

A retrospective cohort study was designed using the National Health Insurance Service—National Health Screening database of Korea. Females over the age of 50 were diagnosed with osteoporosis based on the International Classification of Diseases 10th revision (ICD-10) codes (M80, M81, and M82) with bisphosphonate prescriptions. The cumulative dose of bisphosphonate was calculated using defined daily doses (DDD) to provide an accurate BP cumulative effect on ONJ occurrence. Osteonecrosis of the jaw was identified using both ICD-10 codes and related procedure codes. The incidence rates of ONJ and hazard ratios were estimated according to the bisphosphonate cumulative dose.

Results

Among 74,491 included subjects, 190 cases of ONJ were identified. The incidence rate substantially increased after BP cumulative dose over 1 year (25.75 for DDD < 365, which increased to 53.43 for 365 ≤ DDD < 730). Compared to subjects with a cumulative dose of DDD < 365, subjects with a cumulative dose of 365 ≤ DDD < 730 had 2.36-fold hazard for developing ONJ (p < 0.001).

Conclusion

A bisphosphonate cumulative dose of more than 1 year had an increased risk of ONJ development. A gradual, but not sudden, dose-dependent increase in ONJ risk with BP exposure needs to be considered in providing the optimal BP treatment duration.
Functional Characterization of a Novel Heterozygous Mutation in the Glucokinase Gene That Causes MODY2 in Chinese Pedigrees
Authors: Jiang Feng , Yan Jing , Zhang Rong , Ma Xiaojing , Bao Yuqian , Gu Yujuan , Hu Cheng
Published: December 2021

Background

Glucokinase (GCK) plays a central role in glucose regulation. The heterozygous mutations of GCK can cause a monogenic form of diabetes, maturity-onset diabetes of the young (MODY) directly. In our study, we aimed to explore the mechanism of the novel mutation GCK p.Ala259Thr leading to glucokinase deficiency and hyperglycemia.

Methods

Thirty early-onset diabetes pedigrees were referred to whole exome sequencing for novel mutations identification. Purified wild-type and mutant GCK proteins were obtained from E.coli systems and then subjected to the kinetic and thermal stability analysis to test the effects on GCK activity.

Results

One novel missense mutation GCK p.Ala259Thr was identified and co-segregated with diabetes in a Chinese MODY2 pedigree. The kinetic analysis showed that this mutation result in a decreased affinity and catalytic capability for glucose. The thermal stability analysis also indicated that the mutant protein presented dramatically decreased activity at the same temperature.

Conclusion

Our study firstly identified a novel MODY2 mutation p.Ala259Thr in Chinese diabetes pedigrees. The kinetic and thermal stability analysis confirmed that this mutation caused hyperglycemia through severely damaging the enzyme activities and protein stability.
Flower Color as Predictor for Nectar Reward Quantity in an Alpine Flower Community
Authors: Streinzer Martin , Neumayer Johann , Spaethe Johannes
Published: December 2021

Entomophilous plants have evolved colorful floral displays to attract flower visitors to achieve pollination. Although many insects possess innate preferences for certain colors, the underlying proximate and ultimate causes for this behavior are still not well understood. It has been hypothesized that the floral rewards, e.g., sugar content, of plants belonging to a particular color category correlate with the preference of the flower visitors. However, this hypothesis has been tested only for a subset of plant communities worldwide. Bumble bees are the most important pollinators in alpine environments and show a strong innate preference for (bee) “UV-blue” and “blue” colors. We surveyed plants visited by bumble bees in the subalpine and alpine zones (>1,400 m a.s.l.) of the Austrian Alps and measured nectar reward and spectral reflectance of the flowers. We found that the majority of the 105 plant samples visited by bumble bees fall into the color categories “blue” and “blue-green” of a bee-specific color space. Our study shows that color category is only a weak indicator for nectar reward quantity; and due to the high reward variance within and between categories, we do not consider floral color as a reliable signal for bumble bees in the surveyed habitat. Nevertheless, since mean floral reward quantity differs between categories, naïve bumble bees may benefit from visiting flowers that fall into the innately preferred color category during their first foraging flights.
Genomics and Prognosis Analysis of N6-Methyladenosine Regulators in Lung Adenocarcinoma
Authors: Ma Yanpin , Zhang Huping
Published: December 2021

Objective: N6-methyladenosine (m6A) modification is involved in modulating various biological processes in human cancers. But the implication of m6A modification in lung adenocarcinoma (LUAD) is still unclear. Hence, this study conducted a comprehensive analysis of the expression and clinical implication of m6A regulators in LUAD.

Methods: Consensus clustering analysis of 502 LUAD samples in the TCGA dataset was presented based on the expression profiles of 20 m6A regulators using ConsensusClusterPlus package. Overall survival (OS), activation of signaling pathways and tumor immunity (immune/stromal score, tumor purity, expression of HLA and immune checkpoints, and immune cell infiltration) were compared between m6A modification patterns. The m6A-related genes between patterns were identified and prognostic m6A-related genes were imported into LASSO-cox regression analysis. The m6A risk score was developed and its prognostic implication was evaluated and externally verified in the GSE30219 and GSE72094 dataset. Furthermore, a nomogram that contained independent prognostic indicators was established, followed by external verification.

Results: Two m6A modification patterns were clustered across LUAD based on the expression similarity of the m6A regulators via consensus clustering analysis, with distinct OS, activation of signaling pathways and tumor immunity. Totally, 213 m6A-related genes that were identified by comparing two patterns were significantly related to LUAD prognosis. By LASSO method, we constructed the m6A risk score that was a reliable and independent prognostic factor for LUAD. Patients with low m6A risk score displayed a prominent survival advantage. After incorporating independent clinical features, we developed the prognostic nomogram that exhibited high predictive accuracy and the best clinical net benefit for OS.

Conclusion: Collectively, our study may provide a clinically useful tool for precise prognostic management and optimization of immunotherapeutic strategies for LUAD patients.
MicroRNA-181b-2 and MicroRNA-21-1 Negatively Regulate NF-κB and IRF3-Mediated Innate Immune Responses via Targeting TRIF in Teleost
Authors: Sun Yuena , Zhang Lei , Hong Ling , Zheng Weiwei , Cui Junxia , Liu Xuezhu , Xu Tianjun
Published: December 2021

Upon recognition of bacterial or viral components by Toll-like receptors (TLRs), cells could be activated to induce a series of reactions to produce inflammatory cytokines, type I interferon (IFN), and IFN stimulating genes (ISG). MicroRNAs (miRNAs) are an important regulatory molecules that are widely involved in the regulatory networks of mammalian inflammation and immune responses; however, in lower vertebrates, the regulatory network of miRNA-mediated immune responses is poorly understood. Here, we report two miRNAs form Miichthys miiuy, namely, miR-181b-2 and miR-21-1, that play a negative role in host antiviral and antibacterial immunity. We found that miR-181b-2 and miR-21-1 are abundantly expressed in gram-negative bacteria, as well as RNA rhabdovirus infection. Inducible miR-181b-2 and miR-21-1 suppress the production of inflammatory cytokines and type I IFN by targeting TRIF, thereby avoiding excessive inflammation. We further revealed that miR-181b-2 and miR-21-1 modulate antibacterial and antiviral immunity through the TRIF-mediated NF-κB and IRF3 signaling pathways. The overall results indicate that miR-181b-2 and miR-21-1 act as negative feedback regulators and participate in host antibacterial and antiviral immune responses; this finding could provide information for a deeper understanding of the resistance of lower vertebrates to the invasion of pathogens and to avoidance of excessive immunity.