bluuebunny/crossref_metadata_2025_split huggingface dataset:
Provider Referral Patterns and Surgical Utilization Among New Patients Seen in Spine Clinic
Authors: Araghi Kasra , Subramanian Tejas , Haque Nawaal , Merrill Robert , Amen Troy B. , Shahi Pratyush , Singh Sumedha , Maayan Omri , Sheha Evan , Dowdell James , Iyer Sravisht , Qureshi Sheeraz A. 
Published: April 2023

Study Design.
Retrospective chart review.

Objective:
The objective of this study was to elucidate the demographics of patient referrals from different sources and identify factors that affect a patient’s likelihood of undergoing surgery.

Summary of Background Data.
Despite baseline factors for surgical consideration, such as attempting conservative management, surgeons encounter many patients who are not surgically indicated. Overreferrals, that is, a patient referred to a surgeon that does not need surgery, can result in long wait times, delayed care, worse outcomes, and resource waste.

Materials and Methods.
All new patients at a single academic institution seen in the clinic by eight spine surgeons between January 1, 2018, and January 1, 2022, were analyzed. Referral types included self-referral, musculoskeletal (MSK), and non-MSK provider referral. Patient demographics included age, body mass index (BMI), zip code as a proxy for socioeconomic status, sex, insurance type, and surgical procedures undergone within 1.5 years postclinic visit. Analysis of variance and a Kruskal-Wallis test was used to compare means among normally and non-normally disturbed referral groups, respectively. Multivariable logistic regressions were run to assess demographic variables associated with undergoing surgery.

Results.
From 9356 patients, 84% (7834) were self-referred, 3% (319) were non-MSK, and 13% (1203) were MSK. A statistically significant association with ultimately undergoing surgery was observed with MSK referral type compared with non-MSK referral [odds ratio (OR)=1.37, CI: 1.04–1.82, P=0.0246]. Additional independent variables observed to be associated with patients undergoing surgery included older age (OR=1.004, CI: 1.002–1.007, P=0.0018), higher BMI (OR=1.02, CI: 1.011–1.029, P<0.0001), high-income quartile (OR=1.343, CI: 1.177–1.533, P<0.0001), and male sex (OR=1.189, CI: 1.085–1.302, P=0.0002).

Conclusions.
A statistically significant association with undergoing surgery was observed with a referral by an MSK provider, older age, male sex, high BMI, and a high-income quartile home zip code. Understanding these factors and patterns is critical for optimizing practice efficiency and reducing the burdens of inappropriate referrals.
Severity of non-alcoholic fatty liver disease is a risk factor for developing hypertension from prehypertension
Authors: Song Qirui , Ling Qianhui , Fan Luyun , Deng Yue , Gao Qiannan , Yang Ruixue , Chen Shuohua , Wu Shouling , Cai Jun 
Published: April 2023

Abstract

Background:
There is little published evidence about the role of non-alcoholic fatty liver disease (NAFLD) in the progression from prehypertension to hypertension. This study was conducted to investigate the association of NAFLD and its severity with the risk of hypertension developing from prehypertension.

Methods:
The study cohort comprised 25, 433 participants from the Kailuan study with prehypertension at baseline; those with excessive alcohol consumption and other liver diseases were excluded. NAFLD was diagnosed by ultrasonography and stratified as mild, moderate, or severe. Univariable and multivariable Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident hypertension according to the presence and 3 categories of severity of NAFLD.

Results:
During a median of 12.6 years of follow-up, 10,638 participants progressed to hypertension from prehypertension. After adjusting for multiple risk factors, patients with prehypertension and NAFLD had a 15% higher risk of incident hypertension than those without NAFLD (HR = 1.15, 95% CI 1.10–1.21). Moreover, the severity of NAFLD was associated with the incidence of hypertension, which was higher in patients with more severe NAFLD (HR = 1.15 [95% CI 1.10–1.21] in the mild NAFLD group; HR = 1.15 [95% CI 1.07–1.24] in the moderate NAFLD group; and HR = 1.20 [95% CI 1.03–1.41] in the severe NAFLD group). Subgroup analysis indicated that age and baseline systolic blood pressure may modify this association.

Conclusions:
NAFLD is an independent risk factor for hypertension in patients with prehypertension. The risk of incident hypertension increases with the severity of NAFLD.
Integrative pan-cancer analysis of cuproplasia-associated genes for the genomic and clinical characterization of 33 tumors
Authors: Li Xinyu , Ma Weining , Liu Hui , Wang Deming , Su Lixin , Yang Xitao 
Published: April 2023

Abstract

Background:
The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication.

Methods:
Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)–messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard.

Results:
Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A. In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression (P < 0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs.

Conclusions:
This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
The long non-coding RNA colon cancer-associated transcript 1-Vimentin axis promoting the migration and invasion of HeLa cells
Authors: Li Zhangfu , Yuan Jiangbei , Da Qingen , Yan Zilong , Qu Jianhua , Li Dan , Liu Xu , Zhan Qimin , Liu Jikui 
Published: April 2023

Abstract

Background:
Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1–protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1–protein interaction mediated tumor metastasis.

Methods:
CCAT1–proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1–Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells.

Results:
RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and was participated in the tumor metastasis pathway. Knocked down VIM and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein.

Conclusion:
CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
Superiority of sugammadex in preventing postoperative pulmonary complications
Authors: Liu Haibei , Luo Rong , Cao Shuangjiao , Zheng Bixing , Ye Ling , Zhang Wensheng 
Published: April 2023

Abstract

Background:
Postoperative pulmonary complications often lead to increasing mortality and financial burden. Residual paralysis plays a critical role in postoperative pulmonary complications. This meta-analysis was performed to determine whether sugammadex overmatch neostigmine in reducing postoperative pulmonary complications.

Methods:
PubMed, Embase, Web of Science, Medline through Ovid, Cochrane Library, Wan fang, China National Knowledge Infrastructure, and Chinese BioMedical Literature Databases were searched from their inception to 24 June 2021. Random effects models were used for all analyses. Cochrane risk of bias tool was used to assess the quality of RCTs, while Newcastle Ottawa Quality Assessment Scale was used to assess for the quality of cohort studies.

Results:
Seventeen studies were included in the meta-analysis. Pooled data from cohort studies showed reversing neuromuscular blocking with sugammadex had less risk of compound postoperative pulmonary complications [relative risk (RR): 0.73; 95% confidence interval (CI): 0.60–0.89; P = 0.002; I
2 = 81%], pneumonia (RR: 0.64; 95% CI: 0.48–0.86; I
2 = 42%) and respiratory failure (RR: 0.48, 95% CI: 0.41–0.56, I
2 = 0%). However, pooled data from RCTs did not show any difference between the two groups in pneumonia (RR: 0.58; 95% CI: 0.24–1.40; I
2 = 0%) and respiratory failure. The difference was not found between sugammadex and neostigmine about atelectasis in pooled data from either RCTs (RR: 0.85; 95% CI: 0.69–1.05; I
2 = 0%) or cohort studies (RR: 1.01; 95% CI: 0.87 to 1.18; I
2 = 0%).

Conclusion:
The evidence of superiority of sugammadex was limited by the confounding factors in cohort studies and small scale of RCTs. Whether sugammadex precedes neostigmine in preventing pulmonary complications after surgery is still unknown. Well-designed RCTs with large scale are needed.

Registration:
PROSPERO CRD 42020191575
Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies
Authors: Zhu Tingting , Ding Yantao , Xu Xiaoli , Zhang Liyin , Zhang Xuejun , Cui Yong , Liu Lu 
Published: April 2023

Abstract

Background:
Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.

Methods:
We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.

Results:
We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935–0.987, P = 3.57E−03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936–0.995, P = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941–0.983, P = 5.11E−04; ENEC, OR = 0.964, 95% CI = 0.940–0.989, P = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918–0.986, P = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859–0.976, P = 0.002). The statistical powers of positive MR results were all >0.9.

Conclusion:
This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study
Authors: Hu Xuhua , Zheng Zhaoxu , Han Jing , Li Baokun , Guo Ganlin , Guo Peiyuan , Yang Yang , Li Daojuan , Yan Yiwei , Niu Wenbo , Zhou Chaoxi , Meng Zesong , Feng Jun , Yu Bin , Liu Qian , Wang Guiying 
Published: April 2023

Abstract

Background:
The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection.

Methods:
1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC.

Results:
Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P < 0.001) was a protective factor for the survival of patients. The mean survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients (P < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]).

Conclusions:
IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery.

Trial registration:
chictr.org.cn, ChiCTR 2100043775.
Identification of the metabolic state of surviving cardiomyocytes in the human infarcted heart by spatial single-cell transcriptomics
Authors: Shen Yan , Kim Il-man , Weintraub Neal L. , Tang Yaoliang 
Published: April 2023

Background and purpose:
The metabolic status of surviving cardiomyocytes (CM) in the myocardial tissues of patients who sustained myocardial infarction (MI) is largely unknown. Spatial single-cell RNA-sequencing (scRNA-seq) is a novel tool that enables the unbiased analysis of RNA signatures within intact tissues. We employed this tool to assess the metabolic profiles of surviving CM in the myocardial tissues of patients post-MI.

Methods:
A spatial scRNA-seq dataset was used to compare the genetic profiles of CM from patients with MI and control patients; we analyzed the metabolic adaptations of surviving CM within the ischemic niche. A standard pipeline in Seurat was used for data analysis, including normalization, feature selection, and identification of highly variable genes using principal component analysis (PCA). Harmony was used to remove batch effects and integrate the CM samples based on annotations. Uniform manifold approximation and projection (UMAP) was used for dimensional reduction. The Seurat “FindMarkers” function was used to identify differentially expressed genes (DEGs), which were analyzed by the Gene Ontology (GO) enrichment pathway. Finally, the scMetabolism R tool pipeline with parameters method = VISION (Vision is a flexible system that utilizes a high-throughput pipeline and an interactive web-based report to annotate and explore scRNA-seq datasets in a dynamic manner) and metabolism.type = Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to quantify the metabolic activity of each CM.

Results:
Analysis of spatial scRNA-seq data showed fewer surviving CM in infarcted hearts than in control hearts. GO analysis revealed repressed pathways in oxidative phosphorylation, cardiac cell development, and activated pathways in response to stimuli and macromolecular metabolic processes. Metabolic analysis showed downregulated energy and amino acid pathways and increased purine, pyrimidine, and one-carbon pool by folate pathways in surviving CM.

Conclusions:
Surviving CM within the infarcted myocardium exhibited metabolic adaptations, as evidenced by the downregulation of most pathways linked to oxidative phosphorylation, glucose, fatty acid, and amino acid metabolism. In contrast, pathways linked to purine and pyrimidine metabolism, fatty acid biosynthesis, and one-carbon metabolism were upregulated in surviving CM. These novel findings have implications for the development of effective strategies to improve the survival of hibernating CM within the infarcted heart.
Efficacy and Safety of Different Dosing Regimens of Colchicine in Patients With Coronary Artery Disease: A Network Meta-analysis of 15 Randomized Controlled Trials
Authors: Wang Shixun , Mu Yanguang , Tan Lei , Hao Junqiang 
Published: April 2023

Abstract:
Several meta-analyses have investigated the effects of different doses of colchicine in treating coronary artery disease, but all dosing regimens were never compared in a single study. We aimed to compare the efficacy and safety of 3 dosing regimens of colchicine in patients with coronary artery disease. PubMed, EMBASE, the Cochrane Library, and SCOPUS were searched for randomized controlled trials involving different colchicine doses. Major adverse cardiac events (MACE), all-cause and cardiovascular mortality, recurrent myocardial infarction (MI), stroke, gastrointestinal adverse events (AEs), discontinuation, and hospitalization were evaluated using risk ratio (RR) with 95% confidence interval (CI). A total of 15 randomized controlled trial involving 13,539 patients were included. Pooled results calculated with STATA 14.0 showed that low-dose colchicine significantly reduced MACE (RR, 0.51; 95% CI, 0.32–0.83), recurrent MI (RR, 0.56; 95% CI, 0.35–0.89), stroke (RR, 0.48; 95% CI, 0.23–1.00), and hospitalization (RR, 0.44; 95% CI, 0.22–0.85), whereas high and loading doses significantly increased gastrointestinal AEs (RR, 2.84; 95% CI, 1.26–6.24) and discontinuation (RR, 2.73; 95% CI, 1.07–6.93), respectively. Sensitivity analyses confirmed that 3 dosing regimens did not reduce all-cause and cardiovascular mortality but significantly increased the gastrointestinal AEs, and high dose significantly increased AEs-related discontinuation; loading dose resulted in more discontinuation than low dose. Although differences between 3 dosing regimens of colchicine are not significant, low dose is more effective in reducing MACE, recurrent MI, stroke, and hospitalization than the control, whereas high and loading doses increase gastrointestinal AEs and discontinuation, respectively.
Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers And Guide Surgical Decision Making
Authors: Cardamone Michael S , Hüning Gustavo , Scarlett Chadd , Yin Lu , Luna Alexander J , Franklin Alan J 
Published: April 2023

ABSTRACT

Purpose:
We sought to develop an efficient method for fluorescein angiography (FA) during Digitally Assisted Vitreoretinal Surgery (DAVS).

Methods:
A 485 nm bandpass filter was placed into the filter holder of the accessory light sources of the Constellation Vision System with steel modified washers to produce an exciter source. A barrier filter was placed into the blank slot of a switchable laser filter with a 535 nm bandpass filter and another washer or created digitally with a specific color channel using NGENUITY Software Version 1.4. Fluorescein, 250-500 mg was then injected intravenously during retinal surgery.

Results:
These fluorescence patterns accurately detect many fluorescein angiography biomarkers such as determination of vascular filling times, ischemia, neovascularization, shunt vessels, microaneurysms, and leakage into the vitreous. This enhanced surgical visualization permitted intervention in real time such as laser or diathermy to residual microvascular abnormalities after delamination of retinal neovascularization as well as heavier panretinal laser placement in areas of retinal capillary dropout to relatively preserve areas of more intact retinal microcirculation.

Conclusion:
We are the first to report an efficient method that permits high resolution detection of many classic FA biomarkers such as during DAVS to enhance surgical visualization and intervention in real time.