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Xijuan Xu,1,* Hongan Ying,2,* Xiaozhi Wang,1 Weiwen Hong,1 Meng Zhang3 1Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China; 2Department of Geriatrics, Taizhou First People’s Hospital, Taizhou, People’s Republic of China; 3Department of General Surgery, Taizhou First People’s Hospital, Taizhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiwen Hong, Department of Anus & Intestine Surgery, Taizhou First People’s Hospital, No. 218, Hengjie Road, Huangyan District, Taizhou, Zhejiang Province, People’s Republic of China, Tel/Fax +86-15857666675, Email anyway@wmu.edu.cn Meng Zhang Department of General Surgery, Taizhou First People’s Hospital, Taizhou, 318020, People’s Republic of China, Tel +86 15858687813, Email xuzm04@163.comObjective: This study aims to clarify angiogenesis mechanisms in ulcerative colitis and identify potential therapeutic targets.Methods: The Gene Expression Omnibus (GEO) database was used to obtain expression profiles and clinical data for UC and healthy colon tissues. Angiogenesis-related gene sets were acquired from GeneCards. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) identified UC-associated hub genes. The CIBERSORT algorithm assessed immune cell infiltration. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to determine biological mechanisms. External datasets were utilized to validate and characterize the angiogenesis-related genes in relation to biological agents. Additionally, an ulcerative colitis mouse model was constructed to verify the key genes’ expression using real-time quantitative PCR. To predict potential therapeutic agents, we used the DGIdb database. Molecular docking modeled small molecule binding conformations to key gene targets.Results: This study identified 1,247 DEGs enriched in inflammatory/immune pathways from UC and healthy colon samples. WGCNA indicated the black and light cyan modules were most relevant. Intersecting these with 89 angiogenesis genes revealed 5 UC-associated hub genes (pdgfrb, vegfc, angpt2, tnc, hgf). Validation via ROC analysis, differential expression, and a mouse model confirmed upregulation, supporting their potential as UC diagnostic biomarkers. Bioinformatics approaches like protein–protein interaction, enrichment analysis, and GSEA revealed involvement in PDGFR and PI3K-Akt signaling pathways. CIBERSORT analysis of immune cell infiltration showed positive correlations between the key genes and various immune cells, especially neutrophils, highlighting angiogenesis-inflammation interplay in UC. A ceRNA network was constructed. Drug prediction and molecular docking revealed potential UC therapies like sunitinib and imatinib targeting angiogenesis.Conclusion: This study identified and validated five angiogenesis-related genes (pdgfrb, vegfc, angpt2, tnc, hgf) that may serve as diagnostic biomarkers and drug targets for UC.Keywords: ulcerative colitis, bioinformatics analysis, WGCNA, GSEA, molecular docking

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size.

Huakai Tian,1,&ast; Zitao Liu,2,&ast; Zuo Zhang,3,&ast; Lipeng Zhang,2,&ast; Zhen Zong,2 Jiang Liu,2 Houqun Ying,4 Hui Li5 1Department of General Surgery, First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 2Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 3Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Nuclear Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China; 5Department of Rheumatology and Immunology, First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Department of Rheumatology and Immunology, First Affiliated Hospital of Nanchang University, 17 Yongwai Main Street, Nanchang, 330006, People’s Republic of China, Tel +86-15079108591, Email lihui0791nc@126.com Houqun Ying, Department of Nuclear Medicine, Jiangxi province Key Laboratory of Laboratory Medicine, the Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, 330006, People’s Republic of China, Tel/Fax +86 791-86300410, Email yinghouqun2013@163.comObjective: The aim of this study was to investigate the clinical significance of Fibrinogen and Platelet to Pre-albumin Ratio(FPAR) in predicting the prognosis of patients with advanced gastric cancer(AGC) and to construct a predictive model.Methods: We collected clinical data from 489 postoperative patients with AGC. FPAR was divided into high and low groups according to the receiver operating characteristic (ROC) curve. The value of FPAR in predicting the prognosis of progressive gastric cancer was analysed using univariate and multivariable Cox regression analysis and its relationship with clinicopathological features. Finally, the Overall Survival(OS) and recurrence-free survival(RFS) prediction models were constructed and validated using FPAR.Results: Univariate and multifactorial cox regression analysis showed that grade (P< 0.001), TNM-stage (P< 0.001), chemotherapy (P< 0.001), and FPAR (OR=3.054,95% CI:2.088– 4.467, P< 0.001) were independent risk factors for OS; grade (P=0.021), N-stage (P=0.024), TNM-stage (P=0.033), and FPAR (OR=2.215,95% CI:1.634– 3.003, P< 0.001) were independent risk factors for RFS. Subgroup analysis showed that the FPAR-low group had higher OS and RFS than the FPAR-high group, regardless of the patient’s TNM stage (p< 0.05). However, OS was instead higher in the the stage III-FPAR-low group than in the the stage II-FPAR-high group (p< 0.05), while RFS was not significantly different. Predictive models incorporating FPAR had better predictive performance than those without FPAR, showing wide range of net benefit and AUC. After correction, the 2-year AUC, 3-year AUC and C-index of the OS model were 0.737, 0.756, and 0.746; the 2-year AUC, 3-year AUC, and C-index of the RFS model were 0.738, 0.758, and 0.711.Conclusion: FPAR levels were associated with prognosis in patients with AGC and could independently predict RFS and OS.Keywords: advanced gastric cancer, FPAR, overall survival, recurrence-free survival, prognosis

The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.

Hao Zhang,&ast; Baoting Yu,&ast; Hongsheng Yang, Hongfei Ying, Xiaolong Qu, Lilan Zhu, Cong Wang, Jun Ding Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, 130021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Ding, Department of Radiology, China-Japan Union Hospital of Jilin University, No. 829 of Xinmin Street, Chaoyang District, Changchun, 130021, People’s Republic of China, Tel/Fax +86 04 70 8499 7637, Email dingjun@jlu.edu.cnObjective: To explore the value of 1.5T magnetic resonance (MR) fat saturation-T2-weighted imaging (FS-T2WI) and apparent diffusion coefficient (ADC) imaging texture features in distinguishing the renal changes of patients with stage III type 2 diabetic kidney disease (DKD) from healthy people.Methods: This study collected 55 patients with stage III DKD (39 males and 16 females) and 33 healthy controls (13 males and 20 females) from December 2021 to June 2022 in the China-Japan Union Hospital of Jilin University. All subjects were randomly divided in a ratio of 6:4 to extract and screen the FS-T2WI and ADC texture features of the right kidney of the subjects. The area under the curve (AUC) was used to assess the diagnostic accuracy of each model.Results: There were significant differences between urea, creatinine and sex (p< 0.05) of the two groups in the training and test set, and no significant difference in age and body mass index (BMI). We extracted 1409 imaging features from the original ADC sequence and selected them by wavelet and Laplace-Gaussian filter and LASSO algorithm, and using the same methods of FS-T2WI. Finally, FS-T2WI and ADC models were selected to construct the united model, including 3 first-order features and 8 texture features. The AUC values of the training set of FS-T2WI, ADC, FS-T2WI+ADC combined logistic regression model were 0.96, 0.91, 0.98; the AUC values of the test set were 0.91, 0.89 and 0.93, and the specificity and accuracy values of the united model were 0.90 and 0.89, respectively.Conclusion: FS-T2WI and ADC imaging features based on 1.5 T MR had diagnostic value in the early diagnosis of DKD stage III, and the combined model of FS-T2WI and ADC had high diagnostic efficiency.Keywords: diabetic kidney disease, magnetic resonance imaging, radiomics

Circadian clocks orchestrate daily rhythms in organismal physiology and behavior to promote optimal performance and fitness. In Drosophila, key pacemaker proteins PERIOD (PER) and TIMELESS (TIM) are progressively phosphorylated to perform phase-specific functions. Whereas PER phosphorylation has been extensively studied, systematic analysis of site-specific TIM phosphorylation is lacking. Here, we identified phosphorylation sites of PER-bound TIM by mass spectrometry, given the importance of TIM as a modulator of PER function in the pacemaker. Among the 12 TIM phosphorylation sites we identified, at least two of them are critical for circadian timekeeping as mutants expressing non-phosphorylatable mutations exhibit altered behavioral rhythms. In particular, we observed that CK2-dependent phosphorylation of TIM(S1404) promotes nuclear accumulation of PER-TIM heterodimers by inhibiting the interaction of TIM and nuclear export component, Exportin 1 (XPO1). We propose that proper level of nuclear PER-TIM accumulation is necessary to facilitate kinase recruitment for the regulation of daily phosphorylation rhythm and phase-specific transcriptional activity of CLOCK (CLK). Our results highlight the contribution of phosphorylation-dependent nuclear export of PER-TIM heterodimers to the maintenance of circadian periodicity and identify a new mechanism by which the negative elements of the circadian clock (PER-TIM) regulate the positive elements (CLK-CYC). Finally, because the molecular phenotype of tim(S1404A) non-phosphorylatable mutant exhibits remarkable similarity to that of a mutation in human timeless that underlies familial advanced sleep phase syndrome (FASPS), our results revealed an unexpected parallel between the functions of Drosophila and human TIM and may provide new insights into the molecular mechanisms underlying human FASPS.

To investigate the retinal proteins associated with primary and secondary retinal ganglion cell (RGC) degeneration and explore their molecular pathways, SWATH label-free and target-based mass spectrometry was employed to identify the proteomes in various retinal locations in response to localized optic nerve injury. Unilateral partial optic nerve transection (pONT) was performed on adult Wistar rats and their retinas were harvested 2 weeks later. To confirm the separation of primary and secondary RGC degeneration, immunohistochemistry of RNA binding protein with multiple splicing (RBPMS) and glial fibrillary acidic protein (GFAP) was performed on retinal whole-mounts. Retinal proteomes in the temporal and nasal quadrants were evaluated with high resolution hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS), and SWATH-based acquisition, and their expression was compared to the corresponding retinal quadrant in contralateral control eyes and further validated by multiple reaction monitoring mass spectrometry (MRM-MS). A total of 3641 proteins (FDR < 1%) were identified using QTOF-MS. The raw data are available via ProteomeXchange with the identifier PXD026783. Bioinformatics data analysis showed that there were 37 upregulated and 25 downregulated proteins in the temporal quadrant, whereas 20 and five proteins were upregulated and downregulated, respectively, in the nasal quadrant, respectively (n = 4, p < 0.05; fold change ≥ 1.4-fold or ≤0.7). Six proteins were regulated in both the temporal and the nasal quadrants, including CLU, GFAP, GNG5, IRF2BPL, L1CAM, and CPLX1. Linear regression analysis indicated a strong association between the data obtained by means of SWATH-MS and MRM-MS (temporal, R2 = 0.97; nasal, R2 = 0.96). Gene ontology analysis revealed statistically significant changes in the biological processes and cellular components of primary RGC degeneration. The majority of the significant changes in structural, signaling, and cell death proteins were associated with the loss of RGCs in the area of primary RGC degeneration. The combined use of SWATH-MS and MRM-MS methods detects and quantifies regional changes of retinal protein expressions after localized injury. Future investigation with this integrated approach will significantly increase the understanding of diverse processes of progressive RGC degeneration from a proteomic prospective.

Circadian clocks coordinate time-of-day-specific metabolic and physiological processes to maximize organismal performance and fitness. In addition to light and temperature, which are regarded as strong zeitgebers for circadian clock entrainment, metabolic input has now emerged as an important signal for clock entrainment and modulation. Circadian clock proteins have been identified to be substrates of O-GlcNAcylation, a nutrient sensitive post-translational modification (PTM), and the interplay between clock protein O-GlcNAcylation and other PTMs is now recognized as an important mechanism by which metabolic input regulates circadian physiology. To better understand the role of O-GlcNAcylation in modulating clock protein function within the molecular oscillator, we used mass spectrometry proteomics to identify O-GlcNAcylation sites of PERIOD (PER), a repressor of the circadian transcriptome and a critical biochemical timer of the Drosophila clock. In vivo functional characterization of PER O-GlcNAcylation sites indicates that O-GlcNAcylation at PER(S942) reduces interactions between PER and CLOCK (CLK), the key transcriptional activator of clock-controlled genes. Since we observe a correlation between clock-controlled daytime feeding activity and higher level of PER O-GlcNAcylation, we propose that PER(S942) O-GlcNAcylation during the day functions to prevent premature initiation of circadian repression phase. This is consistent with the period-shortening behavioral phenotype of per(S942A) flies. Taken together, our results support that clock-controlled feeding activity provides metabolic signals to reinforce light entrainment to regulate circadian physiology at the post-translational level. The interplay between O-GlcNAcylation and other PTMs to regulate circadian physiology is expected to be complex and extensive, and reach far beyond the molecular oscillator.

The animal circadian timing system interprets environmental time cues and internal metabolic status to orchestrate circadian rhythms of physiology, allowing animals to perform necessary tasks in a time-of-day-dependent manner. Normal progression of circadian rhythms is dependent on the daily cycling of core transcriptional factors that make up cell-autonomous molecular oscillators. In Drosophila, PERIOD (PER), TIMELESS (TIM), CLOCK (CLK), and CYCLE (CYC) are core clock proteins that function in a transcriptional-translational feedback mechanism to regulate the circadian transcriptome. Posttranslational modifications of core clock proteins provide precise temporal control over when they are active as regulators of clock-controlled genes. In particular, phosphorylation is a key regulatory mechanism that dictates the subcellular localization, stability, and transcriptional activity of clock proteins. Previously, casein kinase 1α (CK1α) has been identified as a kinase that phosphorylates mammalian PER1 and modulates its stability, but the mechanisms by which it modulates PER protein stability is still unclear. Using Drosophila as a model, we show that CK1α has an overall function of speeding up PER metabolism and is required to maintain the 24 h period of circadian rhythms. Our results indicate that CK1α collaborates with the key clock kinase DOUBLETIME (DBT) in both the cytoplasm and the nucleus to regulate the timing of PER-dependent repression of the circadian transcriptome. Specifically, we observe that CK1α promotes PER nuclear localization by antagonizing the activity of DBT to inhibit PER nuclear translocation. Furthermore, CK1α enhances DBT-dependent PER phosphorylation and degradation once PER moves into the nucleus.SIGNIFICANCE STATEMENT Circadian clocks are endogenous timers that integrate environmental signals to impose temporal control over organismal physiology over the 24 h day/night cycle. To maintain the 24 h period length of circadian clocks and to ensure that circadian rhythms are in synchrony with the external environment, key proteins that make up the molecular oscillator are extensively regulated by phosphorylation to ensure that they perform proper time-of-day-specific functions. Casein kinase 1α (CK1α) has previously been identified as a kinase that phosphorylates mammalian PERIOD (PER) proteins to promote their degradation, but the mechanism by which it modulates PER stability is unclear. In this study, we characterize the mechanisms by which CK1α interacts with DOUBLETIME (DBT) to achieve the overall function of speeding up PER metabolism and to ensure proper time-keeping.

Misalignment between lifestyle and the natural day-night cycle, such as mistimed eating, can negatively impact health. Here the authors show that mistimed feeding alters protein O-GlcNAcylation, a nutrient sensitive post-translational modification.

Codon usage bias is a universal feature of all genomes, but its in vivo biological functions in animal systems are not clear. To investigate the in vivo role of codon usage in animals, we took advantage of the sensitivity and robustness of the Drosophila circadian system. By codon-optimizing parts of Drosophila period (dper), a core clock gene that encodes a critical component of the circadian oscillator, we showed that dper codon usage is important for circadian clock function. Codon optimization of dper resulted in conformational changes of the dPER protein, altered dPER phosphorylation profile and stability, and impaired dPER function in the circadian negative feedback loop, which manifests into changes in molecular rhythmicity and abnormal circadian behavioral output. This study provides an in vivo example that demonstrates the role of codon usage in determining protein structure and function in an animal system. These results suggest a universal mechanism in eukaryotes that uses a codon usage "code" within genetic codons to regulate cotranslational protein folding.

Introduction Odontoid peg fractures (OF) are the most common cervical spine fracture in the elderly. This retrospective analysis aimed to compare the outcomes of older patients with OF who had been managed non-operatively with either a hard or soft cervical collar. Materials and Methods We analysed the retrospective data of the clinical and radiographic records of patients 60 years or older who presented over a 10-year period with OF and were treated non-operatively with a cervical collar. Mortality was the primary outcome measure with mechanism of injury, complications, and fracture healing secondary measures. Results 45 patients (hard collar n = 22; soft collar n = 23) were included with comparable demographics for frailty and co-morbidities in each group; age was significantly higher in the soft collar group (80.6 vs 86.4 years; P = .0065). Associated injuries and complications were not significantly different overall, or when Type II fractures were separately analysed ( P = .435 associated injuries, P = .121 complications). All-cause mortality was greater in the soft collar group (30-day mortality hard: 0%, soft: 9%; 1-year mortality hard: 18%, soft: 48% P = .035). However, once corrected for age, this proved not to reach significance ( P = .333) in any fracture type. Non-union was common (77%) but was not significantly different (hard = 70%; soft = 87%; P = .419). Discussion Consistent with other reports, non-union rates remained substantial regardless of which collar was used. After controlling for age, there was no difference in all-cause mortality between elderly patients treated with a hard or soft cervical collar for odontoid peg fractures. Conclusions Soft collars appear suitable for the treatment of odontoid peg fractures in the elderly without compromising outcome. Larger cohort analyses will help confirm this finding.

Purpose: Trampoline parks are becoming popular in many countries, providing recreational facilities for children and adults. This study investigated the effects of trampoline training on knee muscles strength and balance in young adults. Methods: Twenty-six participants (14 males, 12 females) were randomized into trampoline training (TT) and resistance training (RT) groups to undergo a 6-week supervised intervention program (2 × 30 min per week). TT group performed basic trampoline exercises while the RT group performed resistance training targeting lower extremities muscles. Peak knee extension and flexion torque, postural sway characteristics, and Y balance test (YBT) performance were evaluated before and after the intervention. A mixed model analysis of variance (group × time) was applied. Results: After training there were significant improvements in knee extension torque (mean difference[subscript post-pre] [95% CI], TT: 0.27 [0.00, 0.54] N·m/kg, RT: 0.31 [0.09,0.54] N·m/kg, p = 0.001), knee flexion torque (TT: 0.25 [0.17,0.33] N·m/kg, RT: 0.21 [0.08,0.34] N·m/kg, p < 0.001), and dynamic balance (YBT composite scores, mean difference[subscript post-pre] [95% CI], TT: 4.9 [-0.3, 10.2]%, RT: 5.2 [2.4,8.0]%, p = 0.001). No difference between groups was found. Conclusion: Trampoline training can be as effective as resistance training for improving knee muscles strength and dynamic balance in young men and women.

Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription.

This study explored the perceptions of 430 P-12 urban teachers regarding the instruction of diverse students and their own ability to effectively implement culturally responsive teaching (CRT). Employing qualitative methodology, four open-ended sentence stems were used to capture teachers' thoughts, beliefs, and experiences. Results reveal teachers' strong commitment to CRT, an understanding of behaviors which constitute CRT, a strong sense of efficacy in teaching diverse students, and anticipation of positive outcomes through proactively addressing diverse students' needs. This research provides valuable information for school districts and schools of education as they develop culturally responsive teachers for today's diverse classrooms.

The study sought to evaluate a custom intervention programme, informed by the Theory of Planned Behaviour, which aimed to help youth athletes reduce their problematic mobile phone use. A hybrid mixed-methods design was employed in this study, involving a one-group pretest–posttest design and a mixed-methods multiple case study design. 23 Singaporean youth athletes (aged 13–19 years) participated in the intervention programme, and were assessed at pre, post, and follow-up timepoints for their objective and subjective measures of mobile phone use. After the intervention programme had concluded, a smaller sample of eight participants were selected to participate in semi-structured interviews to get their views and feedback on the intervention programme. The results showed that while there were no significant differences in the objective measures of mobile phone use (i.e., duration and frequency) between the timepoints, there was a significant reduction in the subjective measure (i.e., SAS-SV) of problematic mobile phone use in both post and follow-up timepoints. This was supported by the multiple case study analysis, which found that participants were able to implement the various strategies that were taught during the intervention programme, and that those strategies were able to help them reduce their level of problematic mobile phone use. Overall, participant feedback for the intervention programme was positive, with participants stating that it was fun, interactive, relatable, and informative. There were still some barriers that prevented participants from reducing their problematic mobile phone use, and suggestions were given on how to improve the intervention programme in future. [ABSTRACT FROM AUTHOR]

Study Design Retrospective cohort study. Purpose The aim of this study was to identify features associated with increased mortality risk in traumatic C2 fractures in the elderly, including measures of comorbidity and frailty. Overview of Literature C2 fractures in the elderly are of increasing relevance in the setting of an aging global population and have a high mortality rate. Previous analyzes of risk factors for mortality have not included the measures of comorbidity and/or frailty, and no local data have been reported to date. Methods This study comprises a retrospective review of 70 patients of age >65 years at Waikato Hospital, New Zealand with traumatic C2 fractures identified on computed tomography between 2010 and 2016. Demographic details, medical history, laboratory results on admission, mechanism of injury, and neurological status on presentation were recorded. Medical comorbidities were also detailed allowing calculation of the Charlson Comorbidity Index (CCI) and the modified Frailty Index (mFI). Results The most common mechanism of injury was a fall from standing height (n=52, 74.3%). Mortality rates were 14.3% (n=10) at day 30, and 35.7% (n=25) at 1 year. Bivariate analysis showed that both CCI and mFI correlated with 1-year mortality rates. Reduced albumin and hemoglobin levels were also associated with 30-day and 1-year mortality rates. Forward stepwise logistic regression models determined CCI and low hemoglobin as predictors of mortality within 30 days, whereas CCI, low albumin, increased age, and female gender predicted mortality at 1 year. Conclusions The CCI was a useful tool for predicting mortality at 1 year in the patient cohort. Other variables, including common laboratory markers, can also be used for risk stratification, to initiate timely multidisciplinary management, and prognostic counseling for patients and family members.

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.