bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis identifies XRCC4 as a potential immunological and prognostic biomarker associated with pan-cancer
Authors: Yu Yang , Sun Yanyan , Li Zhaoxian , Li Jiang , Tian Dazhi 
Published: February 2023

Abstract
Background
XRCC4 is a NHEJ factor identified recently that plays a vital role in repairing DNA double-stranded breaks. Studies have reported the associations between abnormal expression of XRCC4 and tumor susceptibility and radiosensitivity, but the potential biological mechanisms by which XRCC4 exerts effects on tumorigenesis are not fully understood. This study aimed to systematically investigate the role of XRCC4 across cancer types.

Methods
The TIMER, GTEX and Xiantao Academic database were used to interpret the expression of XRCC4. Genomic alterations and protein expression in human organic and tumor tissues were applied in cBioPortal and the Human Protein Atlas databases. Correlations between XRCC4 expression and immune and molecular subtypes were analyzed by using the TISIDB database. Protein–protein interactions, GO and KEGG enrichment were also applied for XRCC4-related genes. The TIMER and the Tumor Immune Single Cell Hub (TISCH) online databases were used to explore the relationship between XRCC4 and tumor immune microenvironment. Drug sensitivity information was acquired from the CellMiner database to analyze the effect of XRCC4 on sensitivity analysis.

Results
The XRCC4 expression was significantly upregulated in 15 tumor types and downregulated in two tumor types compared with the normal tissues, most of which were validated by the results of Xiantao academic platform. XRCC4 was expressed at intermediate level in malignant cells. The XRCC4 expression was related to the molecular and immune subtypes of human cancers, and the survival outcome of 11 types of cancers, including KIRC, STAD and LIHC. The main type of frequent genetic alteration is amplification. Strong correlations were also found between XRCC4 and immune checkpoint genes in 33 human cancers. Furthermore, the abnormal expression of XRCC4 was related to immune cell infiltration and drug sensitivity. Enrichment analysis showed that XRCC4 was significantly correlated with DNA damage response.

Conclusions
This comprehensive pan-cancer analysis suggested that XRCC4 may play a vital role in the prognosis and immunotherapy response in cancer patients, and it is a promising therapy target in the future.
Operation of national coordinating service for interhospital transfer from emergency departments: experience and implications from Korea
Authors: Min Hye Sook , Sung Ho Kyung , Choi Goeun , Sung Hyehyun , Lee Minhee , Kim Seong Jung , Ko Eunsil 
Published: February 2023

Abstract
Background
Since 2014, Korea has been operating the National Emergency Medical Situation Room (NEMSR) to provide regional emergency departments (EDs) with coordination services for the interhospital transfer of critically ill patients. The present study aimed to describe the NEMSR’s experience and interhospital transfer pattern from EDs nationwide, and investigate the factors related to delayed transfers or transfers that could not be arranged by the NEMSR.

Methods
This study was a retrospective cross-sectional analysis of the NEMSR’s coordination registry from 2017 to 2019. The demographic and hospital characteristics related to emergency transfers were analyzed with hierarchical logistic models.

Results
The NEMSR received a total of 14,003 requests for the arrangement of the interhospital transfers of critically ill patients from 2017 to 2019. Of 10,222 requests included in the analysis, 8297 (81.17%) successful transfers were coordinated by the NEMSR. Transfers were requested mainly due to a shortage of medical staff (59.79%) and ICU beds (30.80%). Delayed transfers were significantly associated with insufficient hospital resources. The larger the bed capacity of the sending hospital, the more difficult it was to coordinate the transfer (odds ratio [OR] for transfer not arranged = 2.04; 95% confidence interval [CI]: 1.48–2.82, ≥ 1000 beds vs. < 300 beds) and the longer the transfer was delayed (OR for delays of more than 44 minutes = 2.08; 95% CI: 1.57–2.76, ≥ 1000 beds vs. < 300 beds).

Conclusions
The operation of the NEMSR has clinical importance in that it could efficiently coordinate interhospital transfers through a protocolized process and resource information system. The coordination role is significant as information technology in emergency care develops while regional gaps in the distribution of medical resources widen.
RETRACTED ARTICLE: Injuries and outcomes resulting due to falls in elderly patients presenting to the Emergency Department of a tertiary care hospital – a cohort study
Authors: Soomar Salman Muhammad , Dhalla Zeyanna 
Published: February 2023

Abstract
Background
Fall injuries and trauma-related hospitalizations are the most common causes of injury and in-hospital stay amongst the elderly population. After the age of 65, the severity and frequency of fall-related problems increases; the repercussions are challenging for senior citizens, caregivers, and healthcare professionals. This study aims to determine the injuries and outcomes resulting from falls in elderly patients presenting to Emergency Department of a tertiary care hospital.

Methods
A cohort study design was used. All elderly patients aged ≥ 60 years who visit the Emergency Department with a history of a fall as a primary complaint presenting to the ED of a tertiary care hospital in Karachi, Pakistan were included. A purposive sampling strategy was used to enroll 318 patients from August 2021 to February 2022. The outcome was risk of mortality. Each individual was followed for 90 days to study the outcome. A multivariable logistic regression was applied to check the association between the outcome and covariates. Crude and adjusted risk ratios were reported. A p-value ≤ 0.05 was considered significant.

Results
Of the 318 participants, 265 (83.3%) were fall injury patients with comorbidities. More than half of the patients in both groups were female [32 (60.4%) & 146 (55.1%)]. Eyeglasses were used by most of the fall patients both without and with comorbidities [21 (39.6%) & 152 (57.4%) p 0.018]. There were multiple reasons for a fall including imbalance/dizziness, which was reported by one third of participants in both groups [15 (28.3%) & 77 (29.1%)] followed by a fall from stairs/steps/escalator [15 (28.3%) & 44 (16.6%) p 0.005]. At the end of one month, of those who had a comorbidity 20 (7.5%) expired. The risk of mortality among fall related injuries in elderly patients who were more than 80 years was 1.48 times (95% CI: 1.20–2.10) more likely when compared to those patients who were younger than 80 years.

Conclusion
Efforts should be made to improve management of the underlying etiology of falls to prevent them in future. The factors that contribute to falls should be identified. Strategies and interventions should be planned to mitigate this risk of fall in elderly to improve their quality of life.
Living arrangement of Indian elderly: a predominant predictor of their level of life satisfaction
Authors: Kandapan Binayak , Pradhan Jalandhar , Pradhan Itishree 
Published: February 2023

Abstract
Objective
This article aims to examine the level of life satisfaction (LS) among Indian older adults and to determine whether their living arrangement is one of the potential determinants of their level of LS.

Methods
Data was drawn from the first and most recent wave of Longitudinal Ageing Study in India conducted in 2017–18. Using the Satisfaction with Life Scale, the level of LS was assessed for 30,370 elderly aged 60 + . Bivariate analysis was carried out to see the variation in the level of LS across elderlies with different socio-demographic characteristics. To investigate the association between LS and living arrangements and the selected socio-demographic factors multinomial logistic regression model was fitted.

Result
The findings reveal that 25.4% and 45.5% of the elderlies have reported having a low and high level of LS, respectively. Living alone was associated with low level of LS. Co-residing with a spouse was associated with a higher likelihood of reporting high level of LS. The study also found that having both spouse and children as coresident increases the likelihood of reporting high level of LS (RRR = 3.15, 95%CI = 2.3–4.28). Elderly with self-reported poor health, limitation in more than two activities of daily living and presence of depressive symptoms were significantly associated with reporting low level of LS. However, being diagnosed with more than three chronic illnesses was associated with high level of LS (RRR = 1.41, 95%CI = 1.25–1.59). Older adults with the following characteristics were more likely to report a lower level of LS: male, 60–64 years old, no or few years of schooling, unmarried, working, rural resident, living in a poor household, Scheduled Caste and Tribe.

Conclusion
The level of life satisfaction in Indian older adults is significantly associated with their living arrangements, thus suggesting that the LS of older adults could be facilitated through interventions that consider their living arrangements. Older adults with various personal and household characteristics were identified as vulnerable groups, who should be the prime targets of the existing welfare policies.
GDNF-RET signaling and EGR1 form a positive feedback loop that promotes tamoxifen resistance via cyclin D1
Authors: Marks Brooke A. , Pipia Ilissa M. , Mukai Chinatsu , Horibata Sachi , Rice Edward J. , Danko Charles G. , Coonrod Scott A. 
Published: February 2023

Abstract
Background
Rearranged during transfection (RET) tyrosine kinase signaling has been previously implicated in endocrine resistant breast cancer, however the mechanism by which this signaling cascade promotes resistance is currently not well described. We recently reported that glial cell-derived neurotrophic factor (GDNF)-RET signaling appears to promote a positive feedback loop with the transcription factor early growth response 1 (EGR1). Here we investigate the mechanism behind this feedback loop and test the hypothesis that GDNF-RET signaling forms a regulatory loop with EGR1 to upregulate cyclin D1 (CCND1) transcription, leading to cell cycle progression and tamoxifen resistance.

Methods
To gain a better understanding of the GDNF-RET-EGR1 resistance mechanism, we studied the GDNF-EGR1 positive feedback loop and the role of GDNF and EGR1 in endocrine resistance by modulating their transcription levels using CRISPR-dCAS9 in tamoxifen sensitive (TamS) and tamoxifen resistant (TamR) MCF-7 cells. Additionally, we performed kinetic studies using recombinant GDNF (rGDNF) treatment of TamS cells. Finally, we performed cell proliferation assays using rGDNF, tamoxifen (TAM), and Palbociclib treatments in TamS cells. Statistical significance for qPCR and chromatin immunoprecipitation (ChIP)-qPCR experiments were determined using a student’s paired t-test and statistical significance for the cell viability assay was a one-way ANOVA.

Results
GDNF-RET signaling formed a positive feedback loop with EGR1 and also downregulated estrogen receptor 1 (ESR1) transcription. Upregulation of GDNF and EGR1 promoted tamoxifen resistance in TamS cells and downregulation of GDNF promoted tamoxifen sensitivity in TamR cells. Additionally, we show that rGDNF treatment activated GDNF-RET signaling in TamS cells, leading to recruitment of phospho-ELK-1 to the EGR1 promoter, upregulation of EGR1 mRNA and protein, binding of EGR1 to the GDNF and CCND1 promoters, increased GDNF protein expression, and subsequent upregulation of CCND1 mRNA levels. We also show that inhibition of cyclin D1 with Palbociclib, in the presence of rGDNF, decreases cell proliferation and resensitizes cells to TAM.

Conclusion
Outcomes from these studies support the hypotheses that GDNF-RET signaling forms a positive feedback loop with the transcription factor EGR1, and that GDNF-RET-EGR1 signaling promotes endocrine resistance via signaling to cyclin D1. Inhibition of components of this signaling pathway could lead to therapeutic insights into the treatment of endocrine resistant breast cancer.
Association between diverticular disease and colorectal cancer: a bidirectional mendelian randomization study
Authors: Zhang Yanxi , Zhang Han , Zhu Jinghan , He Yazhou , Wang Peng , Li Doudou , Liu Xiaozhuan , Jin Wen , Zhang Junxi , Xu Chuan , Yu Zengli , Zhao Xin , Cui Lingling 
Published: February 2023

Abstract
Background:
Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association.

Methods:
Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p < 5 × 10− 8) were selected as instrumental variables from large-scale genome-wide association studies of European descent, respectively. Summary-level data for colon cancer, rectum cancer, and colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium and the UK Biobank study. Summary-level data for diverticular disease was derived from a genome-wide association study conducted in the UK Biobank population. The random effect inverse-variance weighted Mendelian randomization approach was used as the primary method and MR-Egger, weighted-median, and MR-PRESSO approaches were conducted as sensitivity analyses.

Results:
Genetically determined diverticular disease was associated with a higher risk of colorectal cancer (beta = 0.441, 95%CI: 0.081–0.801, P = 0.016) in the FinnGen population, but the association was not found in the UK Biobank (beta = 0.208, 95%CI: -0.291,0.532, P = 0.207). The positive association remained consistent direction in the three sensitivity analyses. In the stratified analysis in the FinnGen consortium, an association was found to exist between genetically predicted diverticular disease and colon cancer (beta = 0.489, 95%CI: 0.020–0.959, P = 0.041), rather than rectum cancer (beta = 0.328, 95%CI: -0.119-0.775, P = 0.151). Besides, we found a slight association between colorectal cancer and diverticular disease (beta = 0.007, 95%CI: 0.004–0.010, P < 0.001) when using colorectal cancer as exposome and diverticular disease as outcome. However, there is a large sample overlap in this step of analysis.

Conclusion:
This Mendelian randomization study suggests that diverticular disease may be a possible risk factor for colorectal cancer and colon cancer rather than rectum cancer in the FinnGen population.
Genetic studies in the Pakistani population reveal novel associations with ventricular septal defects (VSDs)
Authors: Sarwar Sumbal , Shabana  , Sajjad Khadija , Hasnain Shahida 
Published: February 2023

AbstractBackgroundWith prevalence up to 4%, Ventricular Septal Defect (VSD) is one of the leading causes of neonatal deaths. VSD is a common complex genetic disorder that has been associated with many genetic determinants. Variants from genes for the transcription factors including T-BoxTBX5andNFATc1(nuclear factor of activated T cells, cytoplasmic 1), Vascular endothelial growth factor (VEGF), ISLET1 (encoded by theISL1gene) and enzymeMTHFR, a methylene tetrahydrofolate reductase were selected. Genetic risk score (GRS) is a widely accepted approach used to convert the genetic data into prediction and assessment tool for disease susceptibility.MethodsA total of 200 participants were recruited for the current study, 100 VSD patients and 100 controls. Genotyping of theISL1: rs1017,NFATc1: rs7240256,VEGF: rs36208048,TBX5: rs11067075, andMTHFR: rs1801133 variants was performed using tetra primer ARMS PCR and PCR-RFLP. For the statistical analysis, the software SPSS version 23 was used. Genotypic frequencies of cases and controls were calculated using chi-square (χ²) whereas allelic frequencies were calculated by using the SNPStats tool. The association of GRS quartiles with VSD was examined using binary logistic regression. Adjustedp-value 0.01 was used as significance threshold for all analyses.ResultsTheISL1(OD: 0.242, CI: 0.158–0.37,p-value: 2.15 × 10− 4:),NFATc1(OD: 2.53, CI: 1.64–3.89,p-value: 2.11 × 10− 5),TBX5(OD: 2.24, CI: 1.47–3.41,p-value:1.6 × 10− 4) andMTHFR(OD: 10.46, CI: 5.68–19.26,p-value: 2.09 × 10− 9:) variants were found to be in association with VSD. In contrast, theVEGF(OD: 0.952, CI: 0.56–1.62,p-value: 0.8921) variant did not show significance association with the VSD. For cases, the mean GRS score was 3.78 ± 1.285 while in controls it was 2.95 ± 1.290 (p-value: 0.479, CI: 0.474–1.190). Comparison of GRS between cases and control showed that mean GRS of cases was 1.90 ± 0.480 while in controls it was 1.68 ± 0.490 (p-value: 0.001, CI: 0.086–0.354). Higher quartiles were more prevalent in cases whereas lower quartiles were more prevalent in controls.ConclusionGRS of these five loci was strongly associated with VSD. Moreover, genetic risk score can provide better information for the association between variants and disease as compared to a single SNP. We also illustrated that the cumulative power of GRS is greater over the single SNP effect. This is a pilot scale study with a relatively small sample size whose findings should be replicated in a larger sample size for the unique local Pakistani population.
The effect of APN, hs-CRP and APN/hs-CRP in periodontitis with DAA
Authors: Cheng Rui , Xu Xiaojiang , Yang Shurong , mi Zhongqian , Zhao Yong , Wang Chong , Shi Xuexue , Gao Jinhua , Yu Feiyan , Ren Xiuyun 
Published: February 2023

Abstract
Background
Common chronic infections induced low-grade inflammation has been correlated with atherosclerosis as supported by strong evidence. The balance between pro-and anti-inflammatory factors was exploited to elucidate the effects of chronic periodontitis on diabetes-associated atherosclerosis.

Methods
Study subjects encompassed 30 SPF male rats randomly divided into four groups: A group (NC), B group (T2DM), C group (CP), D group (DM + CP). After developing the model, blood samples were collected from the angular vein analyze serum APN, hs-CRP, and blood lipid. the carotid artery was isolated for HE staining.

Result
Compared with group A, the serum APN in group B, C and D decreased gradually with the progression of the disease. Serum hs-CRP in group B, C and D was significantly increased. At T3, T4 and T5 in group B, C and D, APN/hs-CRP significantly decreased. TC, LDL and TG significantly increased in group B, D; HDL significantly decreased in group C. Carotid artery HE staining showed: compared with group A, different degrees of endothelial defect, destruction of elastic fibers in the middle membrane, disorder of smooth muscle arrangement, and partial dissolution 、 fragmentation and Calcium salt deposition necrosis occurred in group B, C and D.

Conclusion
Enhanced systemic inflammation, decreased adiponectin level, and disorganized lipid metabolism with or without type 2 diabetes attributed to local inflammation of periodontitis can result in an imbalance of pro-inflammatory and anti-inflammatory effects. Therefore, it’s more meaningful to predict the progression of DAA with anti-inflammatory/pro-inflammatory variation.
Using a simulation-based approach to promote structured and interactive nursing clinical handover: a pre- and post-evaluation pilot study in bilingual Hong Kong
Authors: Pun Jack 
Published: February 2023

AbstractEffective clinical nursing handover involves the transfer of responsibility and accountability for patient care between nurses, leading to better patient safety and continuity of care. Nurses in bilingual contexts, such as Hong Kong – where nurses are trained in English but communicate in Cantonese – may find it challenging to deliver a safe clinical handover. This article reports a pilot study in which a simulation-based approach is being developed to enhance nursing handover with structured and interactive interactions, using handover protocols such as ISBAR (introduction, situation, background, assessment, recommendation and readback) and CARE-team (connect, ask, respond, empathise) protocols in a bilingual context. The study has a pre‐ and post-evaluation design involving a questionnaire survey before and after a 4‐hour workshop. Fourteen selected bilingual nurses in Hong Kong were trained according to the ISBAR and CARE-team protocols, and their perceptions of complete and structured handovers were evaluated before and after training using the questionnaire. The nurses reported that they were more self-confident in their handover experiences, with a deeper understanding of ISBAR and CARE-team protocols after the simulation-based training intervention, leading to better (i.e., more structured and interactive) clinical handover between nurses. Overall, the staff perceived their handover communication to have improved using simulation-based training.
Transformational leadership and predictors of resilience among registered nurses: a cross-sectional survey in an underserved area
Authors: Abdul Salam Hana’a , Dumit Nuhad Yazbik , Clinton Michael , Mahfoud Ziyad 
Published: February 2023

Abstract
Background
High resilience increases nurses' ability to cope with job-related stressors and enhances job satisfaction and, consequently, their retention. The study aims to identify resilience predictors and perceptions of transformational leadership in a convenience sample of registered nurses in Lebanon.

Methods
An anonymous cross-sectional survey of a convenience sample of 240 registered nurses working for more than a year at three private hospitals in an underserved area in South Lebanon was used. The survey instrument included demographic questions, the True Resilience Scale ©, and the Global Transformational Leadership Scale. Multiple linear regression was used to assess the predictors of resilience after a descriptive analysis of the study variables.

Results
The survey response rate was 85%. The nurses' mean resilience score was 119.4 (SD 15.3), and their perception of transformational leadership score was M = 25.0, SD = 6.8. Compared to bedside nurses, nurse managers, nurses with more than five years of experience, and nurses in critical nursing units had statistically significant higher resilience scores (p < 0.05). Resilience scores and perception of global transformational leadership were moderately correlated (r = 0.53, p < 0.05). In the final multiple linear regression model, 30% of the variation in resilience scores was explained by designation (p < 0.05) and perception of Global Transformational Leadership (p < 0.01). Perception of global transformational leadership scores explained 29% of the variance in resilience scores. Designation and perception of global transformational leadership predicted resilience in this sample.

Conclusions
A national survey of the Lebanese nursing workforce is needed to achieve an improved predictive model and support policy developments to increase resilience among bedside nurses and retain them in the nursing workforce. Nurse administrators can help by strengthening their transformational leadership behaviors. Consistent use of transformational leadership styles will strengthen bedside nurses' resilience, increase nurse retention, and help sustain the Lebanese nursing workforce.