bluuebunny/crossref_metadata_2025_split huggingface dataset:
By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma
Authors: Zhang Pengpeng , Pei Shengbin , Gong Zeitian , Feng Yanlong , Zhang Xiao , Yang Fang , Wang Wei 
Published: January 2023

BackgroundLung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs.MethodsThe most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells.ResultsA total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate.ConclusionThe eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD.
Cranial CT is a mandatory tool to exclude asymptomatic cerebral hemorrhage in elderly patients on anticoagulation
Authors: Schindler Cora R. , Best Alicia , Woschek Mathias , Verboket René D. , Marzi Ingo , Eichler Katrin , Störmann Philipp 
Published: January 2023

BackgroundTraumatic brain injury (TBI) after falls causes death and disability with immense socioeconomic impact through medical and rehabilitation costs in geriatric patients. Diagnosing TBI can be challenging due to the absence of initial clinical symptoms. Misdiagnosis is particularly dangerous in patients on permanent anticoagulation because minimal trauma might result in severe intracranial hemorrhage. The aim of this study is to evaluate the diagnostic necessity of cranial computed tomography (cCT) to rule out intracranial hemorrhage, particularly in the absence of neurologic symptoms in elderly patients on permanent anticoagulation in their premedication.Patients and methodsRetrospective cohort analysis of elderly trauma patients (≥ 65 years) admitted to the emergency department (ED) of the level-1-trauma center of the University Hospital Frankfurt from 01/2017 to 12/2019. The study included patients who suffered a ground-level fall with suspected TBI and subsequently underwent CT because of preexisting anticoagulation.ResultsA total of 227 patients met the inclusion criteria. In 17 of these patients, cCT showed intracranial hemorrhage, of which 14 were subdural hematomas (SDH). In 8 of the patients with bleeding showed no clinical symptoms, representing 5% (n = 160) of all symptom-free patients. Men and women were equally to suffer a post-traumatic hemorrhage. Patients with intracranial bleeding were hospitalized for 14.5 (±10.4) days. Acetylsalicylic acid (ASA) was the most prescribed anticoagulant in both patient cohorts—with or without intracerebral bleeding (70.6 vs. 77.1%, p = 0.539). Similarly, patients taking new oral anticoagulant (NOAC) (p = 0.748), coumarins, or other platelet inhibitors (p &gt; 0.1) did not show an increased bleeding incidence.ConclusionAcetylsalicylic acid and NOAC use are not associated with increased bleeding risk in geriatric trauma patients (≥ 65 years) after fall-related TBI. Even in asymptomatic elderly patients on anticoagulation, intracranial hemorrhage occurs in a relevant proportion after minor trauma to the head. Therefore, cCT is an obligatory tool to rule out cerebral hemorrhage in elderly patients under anticoagulation.
Dynamic changes in fecal microbiota in donkey foals during weaning: From pre-weaning to post-weaning
Authors: Zhang Zhenwei , Huang Bingjian , Gao Xu , Shi Xiaoyuan , Wang Xinrui , Wang Tianqi , Wang Yonghui , Liu Guiqin , Wang Changfa 
Published: January 2023

IntroductionA better understanding of the microbiota community in donkey foals during the weaning transition is a prerequisite to optimize gut function and improve feed efficiency. The objective of the present study was to investigate the dynamic changes in fecal microbiota in donkey foals from pre-to post-weaning period.MethodsA total of 27 fecal samples of donkey foals were collected in the rectum before morning feeding at pre-weaning (30 days of age, PreW group, n = 9), dur-weaning (100 days of age, DurW group, n = 9) and post-weaning (170 days of age, PostW group, n = 9) period. The 16S rRNA amplicon sequencing were employed to indicate the microbial changes during the weaning period.ResultsIn the present study, the cessation of breastfeeding gradually and weaning onto plant-based feeds increased the microbial diversity and richness, with a higher Shannon, Ace, Chao and Sobs index in DurW and PostW than in PreW (p &lt; 0.05). The predominant bacterial phyla in donkey foal feces were Firmicutes (&gt;50.5%) and Bacteroidota (&gt;29.5%), and the predominant anaerobic fungi and archaea were Neocallimastigomycota and Euryarchaeota. The cellulolytic related bacteria including phylum Firmicutes, Spirochaetota and Fibrobacterota and genus norank_f_F082, Treponema, NK4A214_group, Lachnospiraceae_AC2044_group and Streptococcus were increased from pre-to post-weaning donkey foals (p &lt; 0.05). Meanwhile, the functions related to the fatty acid biosynthesis, carbohydrate metabolism and amino acid biosynthesis were significantly enriched in the fecal microbiome in the DurW and PostW donkeys. Furthermore, the present study provided the first direct evidence that the initial colonization and establishment of anaerobic fungi and archaea in donkey foals began prior to weaning. The relative abundance of Orpinomyces were the highest in DurW donkey foals among the three groups (p &lt; 0.01). In terms of archaea, the abundance of Methanobrevibacter were higher in PreW than in DurW and PostW (p &lt; 0.01), but the abundance of Methanocorpusculum were significantly increased in DurW and PostW compared to PreW donkey foals (p &lt; 0.01).DiscussionAltogether, the current study contributes to a comprehensive understanding of the development of the microbiota community in donkey foals from pre-to post-weaning period, which may eventually result in an improvement of the digestion and feed efficiency in donkeys.
A mechanical rotation chair provides superior diagnostics of benign paroxysmal positional vertigo
Authors: Bech Mathias Winther , Staffe Alexander Torp , Hougaard Dan Dupont 
Published: January 2023

BackgroundBenign paroxysmal positional vertigo (BPPV) is the most common vestibular disease. Both therapeutic and diagnostic benefits with mechanical rotation chairs (MRCs) for management of BPPV have been reported. No previous studies have compared diagnostics in MRCs to traditional diagnostics on an examination bed.ObjectiveTo investigate the agreement between BPPV diagnostics performed with an MRC and traditional diagnostics on an examination bed. Secondary objectives were to (1) examine if the two test modalities differ in diagnostic properties when diagnosing largely untreated patients referred from general practitioners (uncomplicated BPPV) compared to patients referred from private ENTs (complicated BPPV) and (2) examine whether impaired participant cooperation during Manual Diagnostics (MDs) alters agreement, sensitivity and specificity.MethodProspective randomized clinical trial in which patients with a case history of BPPV were recruited by referrals from general practitioners, otorhinolaryngologists and other hospital departments in the Northern Region of Denmark. Participants underwent diagnostic examinations twice: once by traditional MDs on an examination bed and once with an MRC. Initial examiner and order of test modality were randomized. Examiners were blinded to each other's findings.ResultsWhen testing the ability to diagnose BPPV, agreement between the two test modalities, was 0.83, Cohen's kappa 0.66. When comparing MD diagnostics to MRC diagnostics (set as gold standard diagnostics following test result interpretation), values for MDs were: sensitivity 71%, specificity 98%, Negative Predictive Value 73%, and Positive Predictive Value 97%. Agreement regarding BPPV subtype classification was found to be 0.71, and Cohen's kappa 0.58. Agreement when isolating the diagnosis to posterior canalolithiasis (p-CAN) was 0.89, Cohen's kappa 0.78.ConclusionDiagnostics, aided by an MRC, are more sensitive than traditional manual BPPV diagnostics. The overall agreement level between test modalities was found to be weak to moderate. When isolating diagnostics to p-CAN, the level of agreement increased to “moderate-strong.” Results also showed higher agreement between test modalities and a significantly higher negative predictive value for MDs when examining patients referred directly from General Practitioners following no- or a single treatment attempt. The diagnostic properties of MDs improved in patients with a higher degree of cooperation.
Older adults and healthcare professionals have limited awareness of the link between the Mediterranean diet and the gut microbiome for healthy aging
Authors: O’Mahony Lauren , O’Shea Emma , O’Connor Eibhlís M. , Tierney Audrey , Harkin Mary , Harrington Janas , Kennelly Sharon , Arendt Elke , O’Toole Paul W. , Timmons Suzanne 
Published: January 2023

ObjectivesStrategies to improve the gut microbiome through consuming an improved diet, including adopting the Mediterranean Diet (MD), may promote healthy aging. We explored older adults’ and healthcare professionals’ (HCPs) perspectives of the MD, gut health, and microbiome for their role in healthy aging.DesignPhenomenological qualitative.SettingCommunity-dwelling older adults and HCPs in primary and secondary care in Ireland.ParticipantsOlder adults (aged 55 + years), recruited through social, retirement and disease-support groups. HCPs recruited through researcher networks and professional associations.MeasurementsSemi-structured 1:1 interviews and focus groups (FGs) conducted remotely with older adults and HCPs separately. Interviews/FGs were recorded, transcribed, and coded using inductive thematic analysis.ResultsForty-seven older adults were recruited (50% male; 49% aged 60–69 years; 28% 70 +), and 26 HCPs including dietitians (n = 8); geriatricians (n = 6); clinical therapists (n = 4); nurses, pharmacists, catering managers, and meal-delivery service coordinators (n = 2 each). Older adults considered the MD “a nice way to enjoy food,” good for cardiovascular health and longevity, but with accessibility and acceptability challenges (increased salads/fish, different food environments, socio-cultural differences). HCPs felt the MD is included in healthy eating advice, but not overtly, mostly through the promotion of mixed-fiber intake. Older adults considered “live” yogurt and probiotics, and to a lesser extent fiber, to maintain a “healthy gut,” suggesting the gut has “something to do with” cognitive and digestive health. Overall, microbiota-health effects were considered “not common knowledge” among most older adults, but becoming more topical among both professionals and the public with advancing scientific communication.ConclusionWhile “gut health” was considered important, specific effects of the MD on gut microbiota, and the significance of this for healthy aging, was under-recognized. Future efforts should explain the importance to older adults of maintaining the gut microbiota through diet, while appreciating perspectives of probiotic products and supplements.
Association between diagnostic efficacy of acoustic radiation force impulse for benign and malignant thyroid nodules and the presence or absence of non-papillary thyroid cancer: A meta-analysis
Authors: Li Jun , Zhang Yu-Rui , Ren Jia-Yu , Li Qiao-Li , Zhu Pei-Shan , Du Ting-Ting , Ge Xiao-Yan , Chen Ming , Cui Xin Wu 
Published: January 2023

PurposeThe aim of this study was to investigate the diagnostic efficacy of Acoustic Radiation Force Impulse (ARFI) for benign and malignant thyroid nodules in the presence and absence of non-papillary thyroid cancer (NPTC) and to determine the cut-off values of Shear Wave Velocity (SWV) for the highest diagnostic efficacy of Virtual Touch Quantification (VTQ) and Virtual Touch Tissue Imaging and Quantification (VTIQ).MethodsThe diagnostic accuracy of ARFI for benign and malignant thyroid nodules was assessed by pooling sensitivity, specificity and area under the curve (AUC) in each group in the presence and absence of both non-papillary thyroid glands, using histology and cytology as the gold standard. All included studies were divided into two groups according to VTQ and VTIQ, and each group was ranked according to the magnitude of the SWV cutoff value to determine the SWV cutoff interval with the highest diagnostic efficacy for VTQ and VTIQ.ResultsA total of 57 studies were collected on the evaluation of ARFI for the diagnosis of benign and malignant thyroid nodules. The results showed that the presence of non-papillary thyroid carcinoma led to differences in the specificity of VTIQ for the identification of benign and malignant thyroid nodules, and the differences were statistically significant. In addition, the diagnostic efficacy of VTQ was best when the cutoff value of SWV was in the interval of 2.48-2.55 m/s, and the diagnostic efficacy of VTIQ was best when the cutoff value of SWV was in the interval of 3.01-3.15 m/s.ConclusionVTQ and VTIQ have a high diagnostic value for benign and malignant thyroid nodules; however, when the malignant nodules in the study contain non-papillary thyroid carcinoma occupying the thyroid gland, the findings should be viewed in a comprehensive manner.
Poly (lactic-co-glycolic acid)-encapsulated iodine-131 nanoparticles fabricated with rhTSH induce apoptosis and immobilization of thyroid cancer cells
Authors: Fan Yongzeng , Xiong Yalan , Wang Xinhong , Chen Jiahao , Fang Danzhou , Huang Jiahui , Yuan Gengbiao 
Published: January 2023

BackgroundAggressive thyroid carcinoma (ATC) usually loses radioiodine avidity to iodine-131 (131I) due to the downregulation of sodium/iodide symporter (NIS). The expression of thyroid stimulating hormone receptor (TSHR) is more persistent than NIS and the administration of recombinant human thyroid stimulating hormone (rhTSH) promotes de novo NIS synthesis. Hence, exploring methods integrating 131I with rhTSH might be a feasible therapeutic strategy for selective delivery of 131I into thyroid cancer to fortify the effect of radioiodine ablation.MethodsThe 131I, poly (lactic-co-glycolic acid) (PLGA) and rhTSH were used to synthesize of the 131I-PLGA-rhTSH nanoparticles. The characteristics of the 131I-PLGA-rhTSH nanoparticles was determined using a light microscopy, scanning electron microscopy (SEM), autoradiography and immunofluorescence (IF) staining. The diameter of the 131I-PLGA-rhTSH nanoparticles was measured with a Mastersizer 3000, and the encapsulation efficiency (EF) of 131I in 131I-PLGA-rhTSH nanoparticles and the radioactivity of a single nanoparticle were determined. Then, the mouse tumor xenograft model was established, and the biodistribution and effect of 131I-PLGA-rhTSH nanoparticles on apoptosis of thyroid cance cells were investigated in vivo. Thereafter, the role of 131I-PLGA-rhTSH nanoparticles in cell viability using cell counting kit-8 and lactate dehydrogenase (LDH) release assays. Subsequently, the underlying mechanism of 131I-PLGA-rhTSH nanoparticles in reducing cell viability was assessed using immunostaining, boyden invasion assays and phalloidin staining.ResultsOur results showed that the method of developing nanoparticles-encapsulated 131I using poly (lactic-co-glycolic acid) (PLGA) and modified with rhTSH (131I-PLGA-rhTSH), was a feasible avenue for the integration of 131I and rhTSH. Meanwhile, the encapsulation efficiency (EF) of 131I-PLGA-rhTSH nanoparticles was approximately 60%, and the radioactivity of a single nanoparticle was about 1.1×10-2 Bq. Meanwhile, the 131I-PLGA-rhTSH nanoparticles were selectively delivered into, gradually enriched and slowly downregulated in xenograft tumor after the administration of 131I-PLGA-rhTSH nanoparticles through tail vein in mouse tumor xenograft model. Thereafter, the tumor weight was significantly reduced after the administration of 131I-PLGA-rhTSH nanoparticles. Subsequently, the application of 131I-PLGA-rhTSH nanoparticles facilitated apoptosis and attenuated immobilization via inhibiting F-actin assembling of FTC-133 cells.ConclusionThe present study develops a suitable approach integrating 131I and rhTSH, and this strategy is a feasible regimen enhancing the effect of radioiodine ablation for the treatment of thyroid cancer.
Identification of thioredoxin-1 as a biomarker of lung cancer and evaluation of its prognostic value based on bioinformatics analysis
Authors: Liu Xiaoting , Dong Xilin , Hu Yaxin , Fang Yanan 
Published: January 2023

BackgroundThioredoxin-1 (TXN), a redox balance factor, plays an essential role in oxidative stress and has been shown to act as a potential contributor to various cancers. This study evaluated the role of TXN in lung cancer by bioinformatics analyses.Materials and methodsGenes differentially expressed in lung cancer and oxidative stress related genes were obtained from The Cancer Genome Atlas, Gene Expression Omnibus and GeneCards databases. Following identification of TXN as an optimal differentially expressed gene by bioinformatics, the prognostic value of TXN in lung cancer was evaluated by univariate/multivariate Cox regression and Kaplan–Meier survival analyses, with validation by receiver operation characteristic curve analysis. The association between TXN expression and lung cancer was verified by immunohistochemical analysis of the Human Protein Atlas database, as well as by western blotting and qPCR. Cell proliferation was determined by cell counting kit-8 after changing TXN expression using lentiviral transfection.ResultsTwenty differentially expressed oxidative stress genes were identified. Differential expression analysis identified five genes (CASP3, CAT, TXN, GSR, and HSPA4) and Kaplan–Meier survival analysis identified four genes (IL-6, CYCS, TXN, and BCL2) that differed significantly in lung cancer and normal lung tissue, indicating that TXN was an optimal differentially expressed gene. Multivariate Cox regression analysis showed that T stage (T3/T4), N stage (N2/N3), curative effect (progressive diseases) and high TXN expression were associated with poor survival, although high TXN expression was poorly predictive of overall survival. TXN was highly expressed in lung cancer tissues and cells. Knockdown of TXN suppressed cell proliferation, while overexpression of TXN enhanced cell proliferation.ConclusionHigh expression of TXN plays an important role in lung cancer development and prognosis. Because it is a prospective prognostic factor, targeting TXN may have clinical benefits in the treatment of lung cancer.
Jumonji domain-containing protein RIOX2 is overexpressed and associated with worse survival outcomes in prostate cancers
Authors: He Chenchen , Liu Wang , Sun Jiahao , Zhang Da , Li Benyi 
Published: January 2023

BackgroundHistone demethylase RIOX2 was cloned as a c-Myc downstream gene involved in cell proliferation and has been implicated as an oncogenic factor in multiple tumor types. Its expression profiles and correlation with disease progression in prostate cancers are unknown.MethodsTranscriptomic profiles of Jumanji domain-containing protein genes were assessed using multiple public expression datasets generated from RNA-seq and cDNA microarray assays. RIOX2 protein expression was assessed using an immunohistochemistry approach on a tissue section array from benign and malignant prostate tissues. Gene expression profiles were analyzed using the bioinformatics software R package. Western blot assay examined androgen stimulation on RIOX2 protein expression in LNCaP cells.ResultsAmong 35 Jumanji domain-containing protein genes, 12 genes were significantly upregulated in prostate cancers compared to benign compartments. COX regression analysis identified that the ribosomal oxygenase 2 (RIOX2) gene was the only one significantly associated with disease-specific survival outcomes in prostate cancer patients. RIOX2 upregulation was confirmed at the protein levels using immunohistochemical assays on prostate cancer tissue sections. Meanwhile, RIOX2 upregulation was associated with clinicopathological features, including late-stage diseases, adverse Gleason scores, TP53 gene mutation, and disease-free status. In castration-resistant prostate cancers (CRPC), RIOX2 expression was positively correlated with AR signaling index but negatively correlated with the neuroendocrinal progression index. However, androgen treatment had no significant stimulatory effect on RIOX2 expression, indicating a parallel but not a causative effect of androgen signaling on RIOX2 gene expression. Further analysis discovered that RIOX2 expression was tightly correlated with its promoter hypomethylation and MYC gene expression, consistent with the notion that RIOX2 was a c-Myc target gene.ConclusionThe Jumanji domain-containing protein RIOX2 was significantly overexpressed in prostate cancer, possibly due to c-Myc upregulation. RIOX2 upregulation was identified as an independent prognostic factor for disease-specific survival.