bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription factor c-Rel regulated by E5 affects the whole process after HPV16 infection through miR-133a-modulated feedback loop aim at mir-379-369 cluster
Authors: Zhou Juan , Li Yongpeng , Xu Ke , Rong Yan , Huang Siting , Wu Hailun , Yi Xianlin , Liu Chanzhen 
Published: December 2022

Abstract
Background
During the development of cervical cancer, HPV infection causes a series of changes in transcription factors and microRNAs. But their relationships with pathogenic processes are not clear.

Methods
Base on previous study, to analyse the relationship among HPV16 infection and the related transcription factors, related miRNAs, so as to further understand the molecular mechanism of HPV16 infection to cervical cancer, around the HPV16 related miRNAs we have reported, the methods of bioinformatics prediction, histology, cell model in vitro and molecular interaction were used for prediction and validation respectively

Results
The results showed that NF-κB family members(c-Rel, p65 and p50) were identified as main HPV16rmiR-transcription factors. They have different expressive characteristics in cervical lesions and play tumorigenesis or progression roles in different periods of HPV16 infection. c-Rel, p65 and p50 act as mediators which link the HPV16 E5 and HPV16 related miRNAs. Among them, c-Rel affects the occurrence and progression of cervical cancer during whole HPV16 infection stage through miR133a-3p–modulated mir-379-369 cluster with a positive feedback way which targeted c-Rel itself and its positive regulator AKT3.

Conclusion
So in the course of HPV16 infection, the E5, c-Rel, and miR-133a-3p form a positive feedback system which aim at mir-379-369 cluster for the whole process from HPV16 infection to cervical cancer.
5-Methoxyflavone alleviates LPS-mediated lung injury by promoting Nrf2-mediated the suppression of NOX4/TLR4 axis in bronchial epithelial cells and M1 polarization in macrophages
Authors: Liang Panqiao , Wang Linxin , Yang Sushan , Pan Xiping , Li Jiashun , Zhang Yuehan , Liang Yueyun , Li Jing , Zhou Beixian 
Published: December 2022

Abstract
Background
Acute lung injury (ALI) arises from sepsis or bacterial infection, which are life-threatening respiratory disorders that cause the leading cause of death worldwide. 5-Methoxyflavone, a methylated flavonoid, is gaining increased attention for its various health benefits. In the current study, we investigated the potential effects of 5-methoxyflavone against LPS-mediated ALI and elucidated the corresponding possible mechanism.

Methods
A mouse model with ALI was established by intratracheal instillation of LPS, and lung pathological changes, signaling pathway related proteins and apoptosis in lung tissues were estimated by H&E staining, immunofluorescence and TUNEL assay, respectively. Cell viability was evaluated by MTT assay; protein levels of pro-inflammatory mediators were measured by ELISA assay; levels of ROS and M1 macrophage polarization were assayed by flow cytometry; the expression of Nrf2 signaling, NOX4/TLR4 axis and P-STAT1 were detected by western blotting.

Results
Our results showed that 5-methoxyflavone treatment inhibited LPS-induced expression of NOX4 and TLR4 as well as the activation of downstream signaling (NF-κB and P38 MAPK), which was accompanied by markedly decreased ROS levels and pro-inflammatory cytokines (IL-6, TNF-α, MCP-1, and IL-8) in BEAS-2B cells. Moreover, we revealed that these effects of 5-methoxyflavone were related to its Nrf2 activating property, and blockade of Nrf2 prevented its inhibitory effects on NOX4/TLR4/NF-κB/P38 MAPK signaling, thus abrogating the anti-inflammatory effects of 5-methoxyflavone. Besides, the Nrf2 activating property of 5-methoxyflavone in RAW264.7 cells led to inhibition of LPS/IFN-γ-mediated STAT1 signaling, resulting in suppression of LPS/IFN-γ-induced M1 macrophage polarization and the repolarization of M2 macrophages to M1. In a mouse model of LPS-induced ALI, 5-methoxyflavone administration ameliorated LPS-mediated lung pathological changes, the increased lung index (lung/body weight ratio), and epithelial cell apoptosis. Meanwhile, we found 5-methoxyflavone effectively suppressed the hyperactive signaling pathways and the production of excessive pro-inflammatory mediators. Moreover, 5-methoxyflavone reduced LPS-mediated M1 macrophage polarization associated with elevated P-STAT1 activation in the lung tissues. In addition, 5-methoxyflavone improved the survival of LPS-challenged mice.

Conclusion
These results indicated that 5-methoxyflavone might be suitable for the development of a novel drug for ALI therapeutic.
Localized DNA tetrahedrons assisted catalytic hairpin assembly for the rapid and sensitive profiling of small extracellular vesicle-associated microRNAs
Authors: Zhang Ye , Li Wenbin , Ji Tingting , Luo Shihua , Qiu Jiuxiang , Situ Bo , Li Bo , Zhang Xiaohe , Zhang Tiange , Wang Wen , Xiao Yunju , Zheng Lei , Yan Xiaohui 
Published: December 2022

AbstractThe profiling of small extracellular vesicle-associated microRNAs (sEV-miRNAs) plays a vital role in cancer diagnosis and monitoring. However, detecting sEV-miRNAs with low expression in clinical samples remains challenging. Herein, we propose a novel electrochemical biosensor using localized DNA tetrahedron-assisted catalytic hairpin assembly (LDT-CHA) for sEV-miRNA determination. The LDT-CHA contained localized DNA tetrahedrons with CHA substrates, leveraging an efficient localized reaction to enable sensitive and rapid sEV-miRNA measurement. Based on the LDT-CHA, the proposed platform can quantitatively detect sEV-miRNA down to 25 aM in 30 min with outstanding specificity. For accurate diagnosis of gastric cancer patients, a combination of LDT-CHA and a panel of four sEV-miRNAs (sEV-miR-1246, sEV-miR-21, sEV-miR-183-5P, and sEV-miR-142-5P) was employed in a gastric cancer cohort. Compared with diagnosis with single sEV-miRNA, the proposed platform demonstrated a higher accuracy of 88.3% for early gastric tumor diagnoses with higher efficiency (AUC: 0.883) and great potential for treatment monitoring. Thus, this study provides a promising method for the bioanalysis and determination of the clinical applications of LDT-CHA.
Graphical Abstract
L-arginine-containing mesoporous silica nanoparticles embedded in dental adhesive (Arg@MSN@DAdh) for targeting cariogenic bacteria
Authors: López-Ruiz Marta , Navas Francisco , Fernández-García Paloma , Martínez-Erro Samuel , Fuentes Mª Victoria , Giráldez Isabel , Ceballos Laura , Ferrer-Luque Carmen Mª , Ruiz-Linares Matilde , Morales Victoria , Sanz Raúl , García-Muñoz Rafael A. 
Published: December 2022

AbstractDental caries is the major biofilm-mediated oral disease in the world. The main treatment to restore caries lesions consists of the use of adhesive resin composites due to their good properties. However, the progressive degradation of the adhesive in the medium term makes possible the proliferation of cariogenic bacteria allowing secondary caries to emerge. In this study, a dental adhesive incorporating a drug delivery system based on L-arginine-containing mesoporous silica nanoparticles (MSNs) was used to release this essential amino acid as a source of basicity to neutralize the harmful acidic conditions that mediate the development of dental secondary caries. The in vitro and bacterial culture experiments proved that L-arginine was released in a sustained way from MSNs and diffused out from the dental adhesive, effectively contributing to the reduction of the bacterial strains Streptococcus mutans and Lactobacillus casei. Furthermore, the mechanical and bonding properties of the dental adhesive did not change significantly after the incorporation of L-arginine-containing MSNs. These results are yielding glimmers of promise for the cost-effective prevention of secondary caries.
Graphical Abstract
Sedentary patterns and cardiometabolic risk factors in Mexican children and adolescents: analysis of longitudinal data
Authors: Aljahdali Abeer A. , Baylin Ana , Ruiz-Narvaez Edward A. , Kim Hyungjin Myra , Cantoral Alejandra , Tellez-Rojo Martha M. , Banker Margaret , Peterson Karen E. 
Published: December 2022

Abstract
Background
Sedentary behavior is a modifiable risk factor for cardiometabolic health; however, the assessment of total sedentary time may not capture youth’s highly active and interrupted activity patterns. This study examined the associations between sedentary activity patterns and cardiometabolic risk factors among Mexican youth, who have a disproportionate burden of metabolic diseases, using a repeated measure design out of a longitudinal data.

Methods
570 subjects in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) birth cohort, who were followed up to three-time points during adolescence, were included. Bout duration, and frequency and percentages of waking time spent in specific intensities of activity, were quantified using ActiGraph wGT3X-BT wrist accelerometers. Self-reported questionnaires were used to query the usual duration of different sedentary behaviors. Outcomes were fasting lipid profile, markers for glucose homeostasis, anthropometry, and blood pressure. Associations were modeled using linear mixed-effects models, and isotemporal substitution approach was additionally used to assess the effect of replacing objectively assessed sedentary activity with other activity intensities, adjusting for potential confounders.

Results
Each hour of self-reported screen-based time was positively associated with diastolic blood pressure (mm Hg) [β = 0.30, 95% confidence interval (95% CI) = 0.10, 0.51], and an hour of other sedentary time was associated with log serum glucose (mg/dL) [β = 0.01, 95% CI = 0.004, 0.017]. Substitution models showed that replacing 5% of sedentary time with moderate to vigorous physical activity (MVPA) was associated with lower waist circumference (cm) [β = − 1.35, 95% CI = − 1.91, − 0.79] and log serum triglycerides (mg/dL) [β = − 0.11, 95% CI = − 0.18, − 0.03]. Substituting one uninterrupted sedentary bout with light activity was associated with lower insulin (μIU/mL) [β = − 0.06, 95% CI = − 0.10, − 0.02].

Conclusions
Sedentary time was associated with cardiometabolic risk factors in Mexican youth in a context-specific manner. Replacing sedentary time with higher intensities was associated with improvements in some cardiometabolic markers.
An AGS-associated mutation in ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the brain
Authors: Guo Xinfeng , Steinman Richard A. , Sheng Yi , Cao Guodong , Wiley Clayton A. , Wang Qingde 
Published: December 2022

Abstract
Background
Aicardi–Goutières syndrome (AGS) is a severe neurodegenerative disease with clinical features of early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in seven protein-coding genes have been found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous.

Methods
Via CRISPR/Cas-9 technology, we established a mutant mouse model in which a genetic mutation found in AGS patients at the ADAR1 coding gene (Adar) loci was introduced into the mouse genome. A mouse model carrying double gene mutations encoding ADAR1 and MDA-5 was prepared using a breeding strategy. Phenotype, gene expression, RNA sequencing, innate immune pathway activation, and pathologic studies including RNA in situ hybridization (ISH) and immunohistochemistry were used for characterization of the mouse models to determine potential disease mechanisms.

Results
We established a mouse model bearing a mutation in the catalytic domain of ADAR1, the D1113H mutation found in AGS patients. With this mouse model, we demonstrated a causative role of this mutation for the early-onset brain injuries in AGS and determined the signaling pathway underlying the neuropathogenesis. First, this mutation altered the RNA editing profile in neural transcripts and led to robust IFN-stimulated gene (ISG) expression in the brain. By ISH, the brains of mutant mice showed an unusual, multifocal increased expression of ISGs that was cell-type dependent. Early-onset astrocytosis and microgliosis and later stage calcification in the deep white matter areas were observed in the mutant mice. Brain ISG activation and neuroglial reaction were completely prevented in the Adar D1113H mutant mice by blocking RNA sensing through deletion of the cytosolic RNA receptor MDA-5.

Conclusions
The Adar D1113H mutation in the ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the mouse brain.
APOE genotype and biological sex regulate astroglial interactions with amyloid plaques in Alzheimer’s disease mice
Authors: Stephen T. L. , Breningstall B. , Suresh S. , McGill C. J. , Pike C. J. 
Published: December 2022

AbstractThe most significant genetic risk factor for developing late-onset Alzheimer’s disease (AD) is the ε4 allele of apolipoprotein E (APOE4). APOE genotype and biological sex are key modulators of microglial and astroglial function, which exert multiple effects on AD pathogenesis. Here, we show astroglial interactions with amyloid plaques in the EFAD transgenic mouse model of AD. Using confocal microscopy, we observed significantly lower levels of astrocytic plaque coverage and plaque compaction (beneficial effects of glial barrier formation) with APOE4 genotype and female sex. Conversely, neurite damage and astrocyte activation in the plaque environment were significantly higher in APOE4 carriers and female mice. Astrocyte coverage of plaques was highest in APOE3 males and poorest in APOE4 females. Collectively, our findings provide new insights into the roles of astroglia and highlight the importance of addressing independent and interactive effects of APOE genotype and biological sex in understanding processes contributing to AD pathogenesis.
Automatic ML-based vestibular gait classification: examining the effects of IMU placement and gait task selection
Authors: Jabri Safa , Carender Wendy , Wiens Jenna , Sienko Kathleen H. 
Published: December 2022

Abstract
Background
Vestibular deficits can impair an individual’s ability to maintain postural and/or gaze stability. Characterizing gait abnormalities among individuals affected by vestibular deficits could help identify patients at high risk of falling and inform rehabilitation programs. Commonly used gait assessment tools rely on simple measures such as timing and visual observations of path deviations by clinicians. These simple measures may not capture subtle changes in gait kinematics. Therefore, we investigated the use of wearable inertial measurement units (IMUs) and machine learning (ML) approaches to automatically discriminate between gait patterns of individuals with vestibular deficits and age-matched controls. The goal of this study was to examine the effects of IMU placement and gait task selection on the performance of automatic vestibular gait classifiers.

Methods
Thirty study participants (15 with vestibular deficits and 15 age-matched controls) participated in a single-session gait study during which they performed seven gait tasks while donning a full-body set of IMUs. Classification performance was reported in terms of area under the receiver operating characteristic curve (AUROC) scores for Random Forest models trained on data from each IMU placement for each gait task.

Results
Several models were able to classify vestibular gait better than random (AUROC > 0.5), but their performance varied according to IMU placement and gait task selection. Results indicated that a single IMU placed on the left arm when walking with eyes closed resulted in the highest AUROC score for a single IMU (AUROC = 0.88 [0.84, 0.89]). Feature permutation results indicated that participants with vestibular deficits reduced their arm swing compared to age-matched controls while they walked with eyes closed.

Conclusions
These findings highlighted differences in upper extremity kinematics during walking with eyes closed that were characteristic of vestibular deficits and showed evidence of the discriminative ability of IMU-based automated screening for vestibular deficits. Further research should explore the mechanisms driving arm swing differences in the vestibular population.
Usability of an exosuit in domestic and community environments
Authors: Basla Chiara , Hungerbühler Irina , Meyer Jan Thomas , Wolf Peter , Riener Robert , Xiloyannis Michele 
Published: December 2022

Abstract
Background
Exosuits have been shown to reduce metabolic cost of walking and to increase gait performance when used in clinical environment. Currently, these devices are transitioning to private use to facilitate independent training at home and in the community. However, their acceptance in unsupervised settings remains unclear. Therefore, the aim of this study was to investigate end-user perspectives and the adoption of an exosuit in domestic and community settings.

Methods
We conducted a mixed-method study to investigate the usability and user experience of an exosuit, the Myosuit. We leveraged on a cohort of seven expert users, who had the device available at home for at least 28 days. Each participant completed two standardized questionnaires (SUS and QUEST) and one personalized, custom questionnaire. Furthermore, a semi-structured interview with each participant was recorded, verbatim transcribed and analyzed using descriptive thematic analysis. Data collected from device sensors quantified the frequency of use.

Results
A mean SUS score of 75.4 out of 100 was reported. Five participants scored above the threshold for above-average usability. Participants also expressed high satisfaction with most of the technical features in the QUEST with an average score of 4.1 (3.86–4.71) out of 5. Participants used the Myosuit mainly for walking outside and exercising at home. However, the frequency of use did not meet the recommendations for physical activity established by the World Health Organization. Five participants used the Myosuit approximately once per week. The two other participants integrated the device in their daily life and used the Myosuit to a greater extent (approx. five times per week). Major factors that prevented an extensive use of the technology were: (i) difficulties in donning that led to (ii) lack of independence and (iii) lack of motivation in exercising.

Conclusions
Although usable for various activities and well perceived, the adoption of the exosuit in domestic and community settings is yet limited. Use outside the clinic poses further challenges that should be considered when developing new wearable robots. Primarily, design should meet the users' claim for independence and increased adjustability of the device.
Evaluation of self-administered antigen testing in a college setting
Authors: Tinker Sarah C. , Prince-Guerra Jessica L. , Vermandere Kelly , Gettings Jenna , Drenzik Cherie , Voccio Gary , Parrott Tonia , Drobeniuc Jan , Hayden Tonya , Briggs Stephen , Heida Debbie , Thornburg Natalie , Barrios Lisa C. , Neatherlin John C. , Madni Sabrina , Rasberry Catherine N. , Swanson Kenneth D. , Tamin Azaibi , Harcourt Jennifer L. , Lester Sandra , Atherton Lydia , Honein Margaret A. 
Published: December 2022

Abstract
Background
The objective of our investigation was to better understand barriers to implementation of self-administered antigen screening testing for SARS-CoV-2 at institutions of higher education (IHE).

Methods
Using the Quidel QuickVue At-Home COVID-19 Test, 1347 IHE students and staff were asked to test twice weekly for seven weeks. We assessed seroconversion using baseline and endline serum specimens. Online surveys assessed acceptability.

Results
Participants reported 9971 self-administered antigen test results. Among participants who were not antibody positive at baseline, the median number of tests reported was eight. Among 324 participants seronegative at baseline, with endline antibody results and ≥ 1 self-administered antigen test results, there were five COVID-19 infections; only one was detected by self-administered antigen test (sensitivity = 20%). Acceptability of self-administered antigen tests was high.

Conclusions
Twice-weekly serial self-administered antigen testing in a low prevalence period had low utility in this investigation. Issues of testing fatigue will be important to address in future testing strategies.
Structure, functions, performance and gaps of event-based surveillance (EBS) in Sudan, 2021: a cross-sectional review
Authors: Malik Elfatih Mohamed , Abdullah Ahmad Izzoddeen , Mohammed Sabir Ali , Bashir Abdelgadir Ali , Ibrahim Rayyan , Abdalla Abdalla Mohammed , Osman Muntasir Mohamed , Mahmoud Tahani Amin , Alkhidir Mohamed Abdalhafiz , Elgorashi Suleiman Gamal , Alzain Mazza Abasher , Mohamed Omer Elbadri , Ismaiel Ismaiel Mohamed , Fadelmula Hatim Fadelalsyeed , Magboul Babiker Ahmed Ali , Habibi Muzhgan , Sadek Mahmoud , Aboushady Ahmed , Lane Christopher 
Published: December 2022

Abstract
Background
Event-based surveillance (EBS) is an essential component of Early Warning Alert and Response (EWAR) as per the International Health Regulations (IHR), 2005. EBS was established in Sudan in 2016 as a complementary system for Indicator-based surveillance (IBS). This review will provide an overview of the current EBS structure, functions and performance in Sudan and identify the gaps and ways forward.

Methods
The review followed the WHO/EMRO guidelines and tools. Structured discussions, observation and review of records and guidelines were done at national and state levels. Community volunteers were interviewed through phone calls. Directors of Health Emergency and Epidemic Control, surveillance officers and focal persons for EBS at the state level were also interviewed. SPSS software was used to perform descriptive statistical analysis for quantitative data, while qualitative data was analysed manually using thematic analysis, paying particular attention to the health system level allowing for an exploration of how and why experiences differ across levels. Written and verbal consents were obtained from all participants as appropriate.

Results
Sudan has a functioning EBS; however, there is an underestimation of its contribution and importance at the national and states levels. The link between the national level and states is ad hoc or is driven by the need for reports. While community event-based surveillance (CEBS) is functioning, EBS from health facilities and from non-health sectors is not currently active. The integration of EBS into overall surveillance was not addressed, and the pathway from detection to action is not clear. The use of electronic databases and platforms is generally limited. Factors that would improve performance include training, presence of a trained focal person at state level, and regular follow-up from the national level. Factors such as staff turnover, income in relation to expenses and not having a high academic qualification (Diploma or MSc) were noticed as inhibiting factors.

Conclusion
The review recommended revisiting the surveillance structure at national and state levels to put EBS as an essential component and to update guidelines and standard operation procedures SOPs to foster the integration between EBS components and the overall surveillance system. The need for strengthening the link with states, capacity building and re-addressing the training modalities was highlighted.