bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hierarchical classification-based pan-cancer methylation analysis to classify primary cancer
Authors: Yang Youpeng , Zeng Qiuhong , Liu Gaotong , Zheng Shiyao , Luo Tianyang , Guo Yibin , Tang Jia , Huang Yi 
Published: December 2023

AbstractHierarchical classification offers a more specific categorization of data and breaks down large classification problems into subproblems, providing improved prediction accuracy and predictive power for undefined categories, while also mitigating the impact of poor-quality data. Despite these advantages, its application in predicting primary cancer is rare. To leverage the similarity of cancers and the specificity of methylation patterns among them, we developed the Cancer Hierarchy Classification Tool (CHCT) using the idea of hierarchical classification, with methylation data from 30 cancer types and 8239 methylome samples downloaded from publicly available databases (The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO)). We used unsupervised clustering to divide the classification subproblems and screened differentially methylated sites using Analysis of variance (ANOVA) test, Tukey-kramer test, and Boruta algorithms to construct models for each classifier module. After validation, CHCT accurately classified 1568 out of 1660 cases in the test set, with an average accuracy of 94.46%. We further curated an independent validation cohort of 677 cancer samples from GEO and assigned a diagnosis using CHCT, which showed high diagnostic potential with generally high accuracies (an average accuracy of 91.40%). Moreover, CHCT demonstrates predictive capability for additional cancer types beyond its original classifier scope as demonstrated in the medulloblastoma and pituitary tumor datasets. In summary, CHCT can hierarchically classify primary cancer by methylation profile, by splitting a large-scale classification of 30 cancer types into ten smaller classification problems. These results indicate that cancer hierarchical classification has the potential to be an accurate and robust cancer classification method.
Magnitude of extended-spectrum β-lactamase and carbapenemase producing Enterobacteriaceae among commonly vended street foods in Arba Minch town, southern Ethiopia
Authors: Alelign Dagninet , Kidanewold Aschalew 
Published: December 2023

Abstract
Background
The rising prevalence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae (ESβL-PE) in street foods poses a significant risk to human health due to its epidemiological significance. Thus, the aim of this study was to determine the magnitude of foodborne Enterobacteriaceae that produce carbapenemase and ESβL, as well as their patterns of antibiotic resistance, in the studied area.

Methods
A community-based cross-sectional study was carried out from January 1st, 2023, to February 30th, 2023. One hundred randomly chosen street-vended food items (one hundred grams of each food item) were aseptically collected, and aliquots of 0.1 ml from the homogenized (25 g of samples into 225 ml of buffered peptone water (BPW)) were inoculated on MacConkey agar and Xylose Lysine Deoxycholate Agar (XLD). Enterobacteriaceae isolates were identified using various biochemical tests. ESβL and carbapenemase were first screened by indicator cephalosporins and carbapenem antibiotics, respectively. ESβL and carbapenemase were confirmed by a double-disc synergy test and modified carbapenem inactivation methods, respectively. Kirby-Bauer disc diffusion method was used for the antimicrobial-resistant test.

Results
A total of 112 Enterobacteriaceae belonging to six different genera were isolated. E. coli was attributed 39 (34.8%), followed by Citrobacter spp. 22 (19.6%) and K. pneumoniae 18 (16.1%), with only 8 (7.1%) isolated Salmonella spp. About 15.2% (n = 17) and 8.9% (n = 10) of Enterobacteriaceae were phenotypically confirmed to be extended-spectrum beta-lactamase (ESβL) and carbapenemase producers, respectively. The highest percentage of ESβL-producing isolates was attributed to K. pneumoniae (n = 5), E. coli (n = 4), and Enterobacter spp. (n = 3). Proteus spp. and Salmonella spp. isolates were carbapenemase-negative. All carbapenemase-positive isolates were found to be ESβL-producers. 70.6% (12/17) of ESβL-producing Enterobacteriaceae were found to be multidrug-resistant (MDR).

Conclusion
A considerable number of multidrug-resistant ESβL and carbapenemase-producing Enterobacteriaceae were identified, suggesting that street foods may be a potential source of MDR foodborne infections. Consequently, it is important to conduct routine examinations of street food items and track trends in medication resistance.
COVID-19 pandemic and initiation of treatment for atrial fibrillation: a nationwide analysis of claims data
Authors: Yang Lanting , Tang Shangbin , He Meiqi , Guo Jingchuan , Gabriel Nico , Swabe Gretchen , Gellad Walid F , Essien Utibe R , Saba Samir , Benjamin Emelia J , Magnani Jared W , Hernandez Inmaculada 
Published: December 2023

Abstract
Background
The COVID-19 pandemic profoundly disrupted the delivery of medical care. It remains unclear whether individuals diagnosed with new onset disease during the pandemic were less likely to initiate treatments after diagnosis. We sought to evaluate changes in the treatment initiation of patients newly diagnosed with atrial fibrillation (AF) after the onset of the COVID-19 pandemic.

Methods
In this retrospective cohort study, we identified individuals with incident AF from 01/01/2016–09/30/2021 using Optum’s de-identified Clinformatics® Data Mart Database. The primary outcome was initiation of oral anticoagulation (OAC) within 30 days of AF diagnosis. Secondary outcomes included initiation of OAC within 180 days of diagnosis, initiation of warfarin, direct oral anticoagulants (DOACs), rhythm control medications and electrical cardioversion within 30 days of diagnosis. We constructed interrupted time series analyses to examine changes in the outcomes following the onset of the pandemic.

Results
A total of 573,524 patients (age 73.0 ± 10.9 years) were included in the study. There were no significant changes in the initiation of OAC, DOAC, and rhythm control medications associated with the onset of the pandemic. There was a significant decrease in initiation of electrical cardioversion associated with the onset of the pandemic. The rate of electronic cardioversion within 30 days of diagnosis decreased by 4.9% per 1,000 patients after the onset of the pandemic and decreased by about 35% in April 2020, compared to April 2019, from 5.53% to 3.58%.

Conclusion
The COVID-19 pandemic did not affect the OAC initiation within 30 days of AF diagnosis but was associated with a decline in the provision of procedures for patients newly diagnosed with AF.
Association between endothelin-1, nitric oxide, and Gensini score in chronic coronary syndrome
Authors: Wang Yujin , Wang Yuqin , Liu Tiaoxia , Qin Yifan , Tang Futian , Zhang Xiaowei , Li Yongnan 
Published: December 2023

Abstract
Background
Chronic coronary syndrome (CCS) is a major public health burden; its pathogenesis involves atherosclerosis and endothelial dysfunction. Endothelin-1 (ET-1) and nitric oxide (NO) are vasoactive substances synthesized by endothelial cells that play a crucial role in CCS development. The Gensini score (GS) is used for evaluating CCS severity based on lumen segment changes, stenosis degree, and coronary stenosis site.

Methods
This prospective study included 71 patients with CCS; we evaluated the relationships between GS and ET-1 and NO serum levels were evaluated in these patients. The GS was calculated for all patients. Serum ET-1 & NO levels among other laboratory parameters were measured.

Results
The high GS group had higher ET-1 and relatively NO expressions in the than the low GS group. GS was positively correlated with ET-1 and negatively correlated with NO, T4, and TSH levels. The results of the multiple linear regression analysis showed that ET-1 had the most significant effect on GS.

Conclusions
We found a strong association between ET-1, NO, and CCS severity. A combination of ET-1, NO, and GS is an essential predictor of CCS disease severity.
Older adults’ experiences of self-determination when needing homecare services—an interview study
Authors: Bölenius Karin , Lämås Kristina , Edvardsson David 
Published: December 2023

Abstract
Background
Self-determination has been shown to be an important factor in mental health and wellbeing, but from the homecare recipients’ point of view, autonomy and self-determination is not fully integrated into homecare services. The aim of this study was to explore older adults’ experiences of self-determination when needing homecare services.

Methods
In 2018, a qualitative descriptive study was conducted and a convenience sample of 15 older adults from 3 homecare service facilities were invited to participate in individual interviews. Data were analysed using qualitative content analyse.

Results
The theme Transitioning from self-determination as independence towards self-determination as shared decision-making emerged through the older adults’ narratives. This ‘transition’ is one in which older adult’s understanding of self-determination and self-esteem was transitioning towards the acceptance of shared decision-making. The person’s inner strength and willingness to make decisions was promoting to enact and preserve independence. Accepting one’s dependence on others and being in a positive atmosphere were described as promoting self-determination and shared decision-making, and vice versa. The above overarching theme permeated all subthemes, which included: mobilising inner strength to enact independence; accepting increasing dependence on others; and being influenced by the atmosphere.

Conclusions
The study contributes increased understanding of older adults’ experiences of self-determination. The results can act as a guide when planning future person-centred care interventions in the context of homecare services and help improve homecare services’ ability to meet the needs of older adults. To summarise, older adults’ reflections on their own self-determination highlighted relationships with other people as important for shared decision-making, which could help preserve older adults’ autonomy and self-esteem.
Association between serum lipoprotein(a) and mildly reduced eGFR: a cross-sectional study
Authors: Zhang Hong , Chen Rui , Xiang Shoukui , Gao Pei , Zhu Jing , Wang Long , Jiang Xiaohong , Hua Fei , Huang Xiaolin 
Published: December 2023

AbstractLipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24–2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05–1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.
Multidimensional analysis to elucidate the possible mechanism of bone metastasis in breast cancer
Authors: Yao Kang , Xiaojun Zhu , Tingxiao Zhao , Shiyao Liao , Lichen Ji , Wei Zhang , Yanlei Li , Jinlong Tian , Xiaoyan Ding , Jun Zhang , Qing Bi , Jun Lv 
Published: December 2023

Abstract
Background
Breast cancer (BC) patients tend to suffer from distant metastasis, especially bone metastasis.

Methods
All the analysis based on open-accessed data was performed in R software, dependent on multiple algorithms and packages. The RNA levels of specific genes were detected using quantitative Real-time PCR as a method of detecting the RNA levels. To assess the ability of BC cells to proliferate, we utilized the CCK8 test, colony formation, and the 5-Ethynyl-20-deoxyuridine assay. BC cells were evaluated for invasion and migration by using Transwell assays and wound healing assays.

Results
In our study, we identified the molecules involved in BC bone metastasis based on the data from multiple BC cohorts. Then, we comprehensively investigated the effect pattern and underlying biological role of these molecules. We found that in the identified molecules, the EMP1, ACKR3, ITGA10, MMP13, COL11A1, and THY1 were significantly correlated with patient prognosis and mainly expressed in CAFs. Therefore, we explored the CAFs in the BC microenvironment. Results showed that CAFs could activate multiple carcinogenic pathways and most of these pathways play an important role in cancer metastasis. Meanwhile, we noticed the interaction between CAFs and malignant, endothelial, and M2 macrophage cells. Moreover, we found that CAFs could induce the remodeling of the BC microenvironment and promote the malignant behavior of BC cells. Then, we identified MMP13 for further analysis. It was found that MMP13 can enhance the malignant phenotype of BC cells. Meanwhile, biological enrichment and immune infiltration analysis were conducted to present the effect pattern of MMP13 in BC.

Conclusions
Our result can improve the understanding of researchers on the underlying mechanisms of BC bone metastasis.
Dynamic profiling of immune microenvironment during anti-PD-1 immunotherapy for head and neck squamous cell carcinoma: the IPRICE study
Authors: Hélène Carinato , Conrad Ombline , Pflumio Carole , Borel Christian , Voegelin Manon , Bernard Alexandre , Schultz Philippe , Onea Mihaela-Alina , Jung Alain , Martin Sophie , Burgy Mickaël 
Published: December 2023

Abstract
Background
Immune checkpoint inhibitors of programmed cell death protein 1 (PD-1) represent a significant breakthrough in treating head and neck squamous cell carcinoma (HNSCC), with long-lasting responses and prolonged survival observed in first- and second-line therapy. However, this is observed in < 20% of patients and high primary/secondary resistance may occur. The primary objective of the identification of predictive factors for the response to anti-PD-1 immunotherapy in head and neck squamous cell carcinoma (IPRICE) study is to identify predictive factors of response to anti-PD-1 immunotherapy.

Methods
The IPRICE study is a single-center, prospective, non-randomized, open-label, and interventional clinical trial. Liquid and tumor biopsies will be performed in 54 patients with recurrent/metastatic (R/M) HNSCC undergoing anti-PD-1 immunotherapy alone to compare the evolution of gene expression and immunological profile between responders and non-responders. We will use a multidisciplinary approach including spatial transcriptomics, single seq-RNA analysis, clinical data, and medical images. Genes, pathways, and transcription factors potentially involved in the immune response will also be analyzed, including genes involved in the interferon-gamma (IFN-γ) pathway, immunogenic cell death and mitophagy, hypoxia, circulating miRNA-mediated immunomodulation, cytokines, and immune repertoire within the tumor microenvironment (TME). With a follow-up period of 3-years, these data will help generate effective biomarkers to define optimal therapeutic strategy and new immunomodulatory agents based on a better understanding of primary/secondary resistance mechanisms. Tumor biopsy will be performed initially before the start of immunotherapy at the first tumor assessment and is only proposed at tumor progression. Clinical data will be collected using a dedicated Case Report Form (CRF).

Discussion
Identifying predictive factors of the response to anti-PD-1 immunotherapy and optimizing long-term immune response require a thorough understanding of the intrinsic and acquired resistance to immunotherapy. To achieve this, dynamic profiling of TME during anti-PD-1 immunotherapy based on analysis of tumor biopsy samples is critical. This will be accomplished through the anatomical localization of HNSCC, which will allow for the analysis of multiple biopsies during treatment and the emergence of breakthrough technologies including single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics.

Trial registration
Clinicaltrial.gov. Registered April 14, 2022, https://www.clinicaltrials.gov/study/NCT05328024.
Carnosine supplementation and retinal oxidative parameters in a high-calorie diet rat model
Authors: de Almeida Torres Rogil Jose , Moreto Fernando , Luchini Andrea , de Almeida Torres Rogerio Joao , Longo Sofia Pimentel , Pinho Ricardo Aurino , Nagashima Seigo , de Noronha Lucia , Ferron Artur Junio Togneri , de Almeida Silva Carol Cristina Vagula , Correa Camila Renata , Aldini Giancarlo , Ferreira Ana Lucia Anjos 
Published: December 2023

Abstract
Background
To assess oxidative effects induced by a high-calorie diet on the retina of Wistar rats and test the antioxidative effects of carnosine supplementation.

Methods
Wistar rats were randomly divided into the following groups: standard diet (SD), high-calorie diet (HcD), standard diet + carnosine (SD + Car), and high-calorie diet + carnosine (HcD + Car). The body weight, adiposity index, plasma glucose, total lipids, high-density lipoprotein (HDL), low-density lipoprotein (LDL), uric acid, creatinine, and triglycerides of the animals were evaluated. The retinas were analyzed for markers of oxidative stress. Hydrogen peroxide production was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCF) oxidation. The total glutathione (tGSH), total antioxidant capacity (TAC), protein carbonyl, and sulfhydryl groups of the antioxidant system were analyzed.

Results
TAC levels increased in the retinas of the SD + Car group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the HcD group (p < 0.05). The levels of GSH and the GSSH:GSSG ratio were increased in the HcD + Car group compared to the SD + Car group (p < 0.05). An increase in the retinal carbonyl content was observed in the HcD group compared to the SD group (p < 0.05) and in the HcD + Car group compared to the SD + Car group (p < 0.05). A high-calorie diet (HcD) was also associated with a decrease in retinal sulfhydryl-type levels compared to the SD group (p < 0.05).

Conclusion
The results suggest that feeding a high-calorie diet to rats can promote an increase in carbonyl content and a reduction in sulfhydryl groups in their retinas. The administration of carnosine was not effective in attenuating these oxidative markers.

Trial registration
Animal Ethics Committee of Botucatu Medical School - Certificate number 1292/2019.
Causal associations between COVID-19 and childhood mental disorders
Authors: Chen Fei , Cao Hongbao , Baranova Ancha , Zhao Qian , Zhang Fuquan 
Published: December 2023

Abstract
Background
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can invade both the peripheral and central nervous systems and impact the function of the brain. Therefore, it is necessary to evaluate the mutual influences between COVID-19 outcomes and childhood mental disorders.

Methods
We examined genetic correlations and potential causalities between three childhood mental disorders and three COVID-19 phenotypes by genetically proxied analyses. The three mental disorders included attention-deficit/hyperactivity disorder (ADHD, N = 292,548), Tourette’s syndrome (TS, N = 14,307), and autism spectrum disorder (ASD, N = 46,350). The three COVID-19 traits included SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Literature-based analysis was used to build gene-based pathways connecting ADHD and COVID-19.

Results
ADHD was positively correlated with the three COVID-19 outcomes (Rg: 0.22 ~ 0.30). Our Mendelian randomization (MR) analyses found that ADHD confers a causal effect on hospitalized COVID-19 (odds ratio (OR): 1.36, 95% confidence interval (CI): 1.10–1.69). TS confers a causal effect on critical COVID-19 (OR: 1.14, 95% CI: 1.04–1.25). Genetic liability to the COVID-19 outcomes may not increase the risk for the childhood mental disorders. Pathway analysis identified several immunity-related genes that may link ADHD to COVID-19, including CRP, OXT, IL6, PON1, AR, TNFSF12, and IL10.

Conclusions
Our study suggests that both ADHD and TS may augment the severity of COVID-19 through immunity-related pathways. However, our results did not support a causal role of COVID-19 in the risk for the childhood mental disorders.
Exploring biomarkers associated with severity of knee osteoarthritis in Southern China using widely targeted metabolomics
Authors: Wang Xiaochao , Cai Wanling , Liu Yihan , Lu Yaoming , Liu Mange , Cao Xuewei , Guo Da 
Published: December 2023

Abstract
Background
Metabolomics is a tool to study the pathogenesis of diseases and their associated metabolites, but there are still insufficient metabolomic studies on severe knee osteoarthritis.To investigate the differences in serum metabolites between healthy populations and knee osteoarthritis (KOA) patients in Southern China using widely targeted metabolomics, and to explore biomarkers and their metabolic pathways that could be associated with the severity of KOA.

Methods
There were 10 healthy individuals in the control group and 32 patients with KOA. According to the Kellgren–Lawrence (KL) grading system, KOA was further divided into mild (n = 13, KL grade 1 and 2) and severe (n = 19, KL grade 3 and 4). Serum samples from all participants were collected and analyzed metabolomics based on ultra-performance liquid chromatography/electrospray ionization/tandem mass spectrometry. We screened for differential metabolites between patients and controls, and between mild and severe KOA. We explored the metabolic pathways involved in differential metabolism using the Kyoto Encyclopedia of Genes and Genomes database.

Results
Sixty-one metabolites were differentially expressed in the sera of the patient group compared with the control group (45 upregulated and 16 downregulated). Analysis of the mild and severe KOA groups showed a total of 12 differential metabolites. Receiver operating characteristic curve analysis showed N-alpha-acetyl-L-asparagine was a good predictor of advanced osteoarthritis(OA).Differential metabolites are enriched in multiple pathways such as arachidonic acid metabolism.

Conclusion
Widely targeted metabolomics found that upregulation of the amino acid metabolite N-α-acetyl-L-asparagine was significantly associated with severe KOA and could be a biomarker for predicting severity of KOA. Arachidonic acid metabolism may play an important role in patients with severe KOA.