bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dentoalveolar, skeletal, pharyngeal airway, cervical posture, hyoid bone position, and soft palate changes with Myobrace and Twin-block: a retrospective study
Authors: Çoban Büyükbayraktar Zeynep , Camcı Hasan 
Published: January 2023

AbstractBackgroundThe primary aim of this study was to evaluate the dentoalveolar, skeletal, pharyngeal airway, cervical posture, hyoid bone position, and soft palate effects of the Myobrace and Twin-block appliances. The second was to compare them in terms of ease of use by assessing the factors that may influence patient compliance.MethodsThe study included thirty-six Class II division 1 patients (19 females, 17 males; mean age, 12.14 ± 1.23) who had previously been treated in the Orthodontic Clinic at Sivas Cumhuriyet University Faculty of Dentistry. The patients were divided into two groups: Group 1: Myobrace (n = 18), and Group 2: twin block (n = 18). The effects of the appliances on the skeletal, dentoalveolar, soft tissue, craniocervical, and other anatomic structures were assessed using 46 measurements (22 linear and 24 angular), on pre and post-treatment cephalometric radiographs. AudaxCeph 5.0 software (Ljubljana, Slovenia) was used for the analysis. To analyze the changes after one year of treatment, a paired sample t-test and Wilcoxon signed-rank test were used. Intergroup comparison was performed using the Student t-test and the Mann–Whitney U test.ResultsIn the Myobrace and Twin-block groups, there was a significant increase in SNB (°) (p = 0.004,p = 0.001), IMPA (°) (p = 0.005,p = 0.001) and a significant drop in U1/SN (°) (p = 0.021,p = 0.005). The lengths of Cd–Gn (mm), Go–Pg (mm), and Cd–Go (mm) increased significantly in the Twin-block group (p = 0.003,p = 0.010,p = 0.001), whereas the Myobrace group did not change. Similarly, there was no significant difference in pharyngeal and soft palate measurements in the Myobrace group but a statistically significant decrease in SP length and angle in the Twin-block group (p = 0.001,p = 0.006). Increases in SN/OPT (°) (p = 0.032,p = 0.001) and SN/CVT (°) (p = 0.012,p = 0.001) were statistically significant in both groups. Myobrace was more difficult to use while sleeping, whereas the twin block caused more nausea.ConclusionsBoth appliances can be used for mandibular advancement. The Twin-block appliance, on the other hand, was more effective and patient-friendly.
Work experience was associated with the knowledge and practice of catheter-associated urinary tract infection prevention among nurses at University of Gondar Comprehensive Specialized Hospital, northwest Ethiopia, 2021
Authors: Zegeye Alebachew Ferede , Kassahun Chanyalew Worku , Temachu Yemataw Zewdu 
Published: January 2023

Abstract
Background
Catheter-associated urinary tract infection is the source of about 20% of episodes of health-care acquired infections in acute care facilities and it is over 50% in long-term care facilities. In Ethiopia, there is no published scientific research regarding knowledge and practice of nurses on catheter-associated urinary tract infections prevention. Therefore, this study aimed to assess knowledge, practice and associated factors of CAUTI prevention among nurses working at university of Gondar comprehensive specialized hospital, northwest Ethiopia, 2021.

Methods
Institutional based cross sectional study was conducted at University of Gondar Comprehensive Specialized Referral Hospital from April 01 to May 01, 2021 among 423 nurses. Simple random sampling technique was used. Data were collected by using self-administered questionnaire then coded and entered into EPI- Data version 4.6 and then exported to SPSS version 23. Descriptive statistics was computed, and the result was summarized by texts, tables, and charts. All variables with P-value < 0.25 in the univariate analysis were included in the multivariable regression analysis. The degree of association was interpreted by using the adjusted odds ratio with 95% confidence intervals.

Results
Good knowledge and practice of nurses towards CAUTI prevention was 37.7% and 51.8% respectively. Good knowledge was associated with sex [AOR = 1.84, 95% CI (1.09, 3.11)], work experience [AOR = 2.36, 95% CI (1.09, 5.10)], working unit [AOR = 6.9, 95% CI (2.11, 22.52)], training [AOR = 2.33, 95% CI (1.17, 4.65)] and had guideline [AOR = 2.78, 95% CI (1.59, 4.88)]. Good practice was associated with sex, work experience, attitude and knowledge towards CAUTI prevention [AOR = 2.19, 95% CI (1.23, 3.88)], [AOR = 5.44, 95% CI (1.66, 17.84)], [AOR = 3.06, 95% CI (1.65, 5.67)], and [AOR = 5.28, 95% CI (2.86, 9.76)] respectively.

Conclusions
Nearly one-third of nurses had good knowledge and more than half of nurses had good practice towards CAUTI prevention. Sex, work experience, work unit, presence of guideline, and training were significantly associated with knowledge. Sex, work experience, good attitude and, knowledge were associated with practice of nurses towards CAUTI prevention. The knowledge and practice towards catheter associated urinary tract infection prevention among nurses should be increased, so that the patients could enjoy and maintain the healthy lifestyle.
Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease
Authors: Nishikido Toshiyuki 
Published: January 2023

AbstractElevated low-density lipoprotein cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease. Although high-intensity lipid-lowering therapies with statins and ezetimibe are highly effective for reducing LDL-C levels, over half of high-risk patients do not achieve guideline-recommended LDL-C goals. Thus, there is a significant gap between treatment guidelines and their implementation in daily clinical practice. The major causes are individual variability in the response to lipid-lowering therapies and variation in treatment adherence. Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies combined with statins provide marked and consistent reduction in LDL-C levels; however, poor adherence due to the need for subcutaneous injections every 2 or 4 weeks and high cost are major obstacles to their use in real-world clinical settings. Inclisiran, a recently approved novel small interfering ribonucleic acid (siRNA) molecule that inhibits PCSK9 synthesis, provides robust and long-term reduction in LDL-C levels with a low inter-individual variability in the LDL-C-lowering response. Moreover, its administration by biannual injection is expected to greatly improve treatment adherence. Clinical trials of this drug lasting for up to 4 years showed acceptable safety profiles, and ongoing studies accumulate evidence of its longer-term safety. This narrative review summarizes the available evidence on the efficacy and safety of inclisiran and analyzes its potential to overcome the gap between guideline recommendations and real-world clinical practice in current LDL-C-lowering therapies, with a focus on reduced LDL-C level variability and improved treatment adherence.
Association between triglyceride-glucose index and risk of cardiovascular disease among postmenopausal women
Authors: Liu Qian , Si Fei , Liu Zhou , Wu Yuntao , Yu Jing 
Published: January 2023

Abstract
Objective
We aimed to examine the association of triglyceride-glucose index (TyG) with risk for cardiovascular disease (CVD) among postmenopausal women.

Methods
A total of 7741 participants met the inclusion criteria, and were included in the analysis. The TyG index was calculated as ln (triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2). The participants were classified into four groups by the quartiles of TyG index, and the Q1 group was used as the reference group. The cumulative incidence of CVD for the groups were compared using the Kaplan–Meier curves. The association between the TyG index and risk of CVD among postmenopausal women was assessed by the Cox proportional hazards models (hazard ratio [HR], 95% confidence intervals [CI]).

Results
During a median follow-up of 12 years, a total of 383 (4.95%) participants developed incident CVD. After adjusting for potential confounding factors, a high baseline TyG index (Q4 group) was associated with higher future risk of CVD, the HR (95% CI) of CVD risk was 1.70 (1.21–2.38) in Q4 group compared with the Q1 group. Subgroup analyses showed the Q4 group was significantly associated with the risk of CVD, regardless of age at menopause (younger than 50 years; 50 years and older) and obesity status.

Conclusions
Higher TyG index at baseline as a marker of insulin resistance (IR), is associated with higher risk of future CVD among postmenopausal women. The TyG index may serve as a simple and easy marker for early identification of high-risk individuals in the postmenopausal women.
New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma
Authors: Shen Guqun , Li Fen , Wang Yan , Huang Yongmei , Aizezi Gulibiya , Yuan Jinrui , Ma Cailing , Lin Chen 
Published: January 2023

Abstract

Background
N6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC.

Methods
We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP.

Results
METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A “reader” YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2.

Conclusions
In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.
Impact of the gut microbiota and associated metabolites on cardiometabolic traits, chronic diseases and human longevity: a Mendelian randomization study
Authors: Gagnon Eloi , Mitchell Patricia L. , Manikpurage Hasanga D. , Abner Erik , Taba Nele , Esko Tõnu , Ghodsian Nooshin , Thériault Sébastien , Mathieu Patrick , Arsenault Benoit J. 
Published: January 2023

AbstractFeatures of the gut microbiota have been associated with several chronic diseases and longevity in preclinical models as well as in observational studies. Whether these relations underlie causal effects in humans remains to be established. We aimed to determine whether the gut microbiota influences cardiometabolic traits as well as the risk of chronic diseases and human longevity using a comprehensive 2-Sample Mendelian randomization approach. We included as exposures 10 gut-associated metabolites and pathways and 57 microbial taxa abundance. We included as outcomes nine cardiometabolic traits (fasting glucose, fasting insulin, systolic blood pressure, diastolic blood pressure, HDL cholesterol, LDL cholesterol, triglycerides, estimated glomerular filtration rate, body mass index [BMI]), eight chronic diseases previously linked with the gut microbiota in observational studies (Alzheimer’s disease, depression, type 2 diabetes, non-alcoholic fatty liver disease, coronary artery disease (CAD), stroke, osteoporosis and chronic kidney disease), as well as parental lifespan and longevity. We found 7 associations with evidence of causality before and after sensitivity analyses, but not after multiple testing correction (1198 tests). Most effect sizes (4/7) were small. The two largest exposure-outcome effects were markedly attenuated towards the null upon inclusion of BMI or alcohol intake frequency in multivariable MR analyses. While finding robust genetic instruments for microbiota features is challenging hence potentially inflating type 2 errors, these results do not support a large causal impact of human gut microbita features on cardiometabolic traits, chronic diseases or longevity. These results also suggest that the previously documented associations between gut microbiota and human health outcomes may not always underly causal relations.
Pan-cancer onco-signatures reveal a novel mitochondrial subtype of luminal breast cancer with specific regulators
Authors: Simeone Ines , Ceccarelli Michele 
Published: January 2023

Abstract
Background
Somatic alterations in cancer cause dysregulation of signaling pathways that control cell-cycle progression, apoptosis, and cell growth. The effect of individual alterations in these pathways differs between individual tumors and tumor types. Recognizing driver events is a complex task requiring integrating multiple molecular data, including genomics, epigenomics, and functional genomics. A common hypothesis is that these driver events share similar effects on the hallmarks of cancer. The availability of large-scale multi-omics studies allows for inferring these common effects from data. Once these effects are known, one can then deconvolve in every individual patient whether a given genomics alteration is a driver event.

Methods
Here, we develop a novel data-driven approach to identify shared oncogenic expression signatures among tumors. We aim to identify gene onco-signature for classifying tumor patients in homogeneous subclasses with distinct prognoses and specific genomic alterations. We derive expression pan-cancer onco-signatures from TCGA gene expression data using a discovery set of 9107 primary pan-tumor samples together with respective matched mutational data and a list of known cancer-related genes from COSMIC database.

Results
We use the derived ono-signatures to state their prognostic significance and apply them to the TCGA breast cancer dataset as proof of principle of our approach. We uncover a “mitochondrial” sub-group of Luminal patients characterized by its biological features and regulated by specific genetic modulators. Collectively, our results demonstrate the effectiveness of onco-signatures-based methodologies, and they also contribute to a comprehensive understanding of the metabolic heterogeneity of Luminal tumors.

Conclusions
These findings provide novel genomics evidence for developing personalized breast cancer patient treatments. The onco-signature approach, demonstrated here on breast cancer, is general and can be applied to other cancer types.
ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway
Authors: Xu Jinming , Wang Yan , Jiang Jiahao , Yin Cong , Shi Bentao 
Published: January 2023

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear.

Methods
We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments.

Results
ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT.

Conclusions
High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.
The presence of cerebellar B cell aggregates is associated with a specific chemokine profile in the cerebrospinal fluid in a mouse model of multiple sclerosis
Authors: Schropp Verena , Chunder Rittika , Dietel Barbara , Tacke Sabine , Kuerten Stefanie 
Published: January 2023

Abstract
Background
The presence of meningeal ectopic lymphoid structures (ELS) in a subgroup of patients diagnosed with secondary progressive multiple sclerosis (SPMS) corresponds to a pronounced cortical inflammation and an aggravated disease course. In MP4-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), B cell aggregates develop in the central nervous system (CNS) in the chronic stage of the disease. Therefore, the model is suitable for studying key molecules of ELS development and maintenance. Here, we investigated whether there is a specific cytokine and chemokine signature in paired cerebrospinal fluid (CSF) and serum samples associated with the presence of cerebellar B cell and T cell pathology and B cell aggregates of MP4-immunized mice.

Methods
Paired CSF and serum samples were collected from the cisterna magna and periphery of MP4-immunized mice at the chronic stage of disease. A control group with mice immunized only with the adjuvant (vehicle) was included in the study. A selected panel of 34 cytokines and chemokines were measured by MAGPIX® for both cohorts. For the assessment of B cell and T cell infiltration, immunohistochemical staining was performed and analyzed using light microscopy. To detect specific chemokine receptors additional staining was conducted.

Results
While we detected several upregulated cytokines and chemokines in the CSF of MP4-immunized mice independent of the extent of B cell and T cell pathology compared to vehicle-immunized mice, C-C motif chemokine ligand (CCL)-1 was associated with high B cell and T cell infiltration. Furthermore, the level of certain chemokines, including CCL1, CCL5, CCL7, CCL12, CCL22 and C-X-C motif chemokine ligand (CXCL)-13, was significantly increased (p < 0.05) in MP4-immunized mice showing a high number of B cell aggregates. While C-C motif chemokine receptor (CCR)5 had a ubiquitous expression independent of the extent of B cell and T cell pathology, C-X-C motif chemokine receptor (CXCR)-5 and CXCR6 expression was specifically associated with high B cell and T cell pathology.

Conclusion
Our data suggest that multiple cytokines and chemokines are involved in the pathophysiology of MP4-induced EAE. Furthermore, the presence of B cell aggregates was associated with a specific chemokine profile in the CSF, which might be useful for predicting the presence of these aggregates without the necessity to histologically screen the CNS tissue.
Nanoparticulate MgH2 ameliorates anxiety/depression-like behaviors in a mouse model of multiple sclerosis by regulating microglial polarization and oxidative stress
Authors: Li Zhenghao , Chen Kefu , Shao Qi , Lu Hongtao , Zhang Xin , Pu Yingyan , Sun Xuejun , He Hua , Cao Li 
Published: January 2023

AbstractMultiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Anxiety and depression are the most common psychiatric comorbidities of MS, which seriously affect patients’ quality of life, treatment compliance, and prognosis. However, current treatments for anxiety and depression in MS show low therapeutic efficacy and significant side effects. In the present study, we explored the therapeutic effects of a novel low-toxic anti-inflammatory drug, nanoparticulate magnesium hydride (MgH2), on mood disorders of MS. We observed that anxiety/depression-like behaviors in experimental autoimmune encephalomyelitis (EAE) mice were alleviated by MgH2 treatment. In addition, disease severity and inflammatory demyelination were also diminished. Furthermore, we confirmed the suppressive effect of MgH2 on depression in the acute restraint stress model. Mechanistically, MgH2 may play a therapeutic role by promoting microglial M2 polarization, inhibiting microglial M1 polarization, and reducing oxidative stress and mitochondrial damage. Therefore, nanoparticulate MgH2 may be a promising therapeutic drug for psychiatric comorbidities of MS.
Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals
Authors: Byappanahalli Anjali M. , Noren Hooten Nicole , Vannoy Mya , Mode Nicolle A. , Ezike Ngozi , Zonderman Alan B. , Evans Michele K. 
Published: January 2023

Abstract
Background
Frailty, a clinical syndrome commencing at midlife, is a risk for morbidity and mortality. Little is known about the factors that contribute to the chronic inflammatory state associated with frailty. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released into the circulation and are mediators of intercellular communication. We examined whether mitochondrial DNA (mtDNA) and inflammatory proteins in EVs may act as damage-associated molecular pattern (DAMP) molecules in frailty.

Results
To address whether EVs and their associated mtDNA and inflammatory protein cargo are altered with frailty, EVs were isolated from non-frail (n = 90) and frail (n = 87) middle-aged (45–55 years) participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. EV concentration was highest in frail White participants. EV mtDNA levels were significantly higher in frail individuals compared to non-frail individuals. The presence of six inflammatory proteins in EVs (FGF-21, HGF, IL-12B, PD-L1, PRDX3, and STAMBP) were significantly associated with frailty. EV inflammatory proteins were significantly altered by frailty status, race, sex, and poverty status. Notably, frail White participants had higher levels of EV-associated CD5, CD8A, CD244, CXCL1, CXCL6, CXCL11, LAP-TGF-beta-1 and MCP-4 compared to frail and non-frail African American participants. Frail White participants living below poverty had higher levels of EV-associated uPA. EV-associated CCL28 levels were highest in non-frail women and CXCL1 were highest in non-frail men. Men living below poverty had higher levels of CD5, CD8A, CXCL1, LAP-TGF-beta-1, and uPA. CXCL6 levels were significantly higher in individuals living above poverty. There was a significant correlation between EV mtDNA levels and the presence of inflammatory proteins.

Conclusions
These data suggest that mtDNA within EVs may act as a DAMP molecule in frailty. Its association with chemokines and other inflammatory EV cargo proteins, may contribute to the frailty phenotype. In addition, the social determinant of health, poverty, influences the inflammatory cargo of EVs in midlife.