bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty quantification of computational fluid dynamics-based predictions for fractional flow reserve and wall shear stress of the idealized stenotic coronary
Authors: Ho Nghia Nguyen , Lee Kwan Yong , Lee Sang-Wook 
Published: November 2023

IntroductionIn clinical practice, hemodynamics-based functional indices, such as fractional flow reserve (FFR) and wall shear stress (WSS), are useful in assessing the severity and risk of rupture of atherosclerotic lesions. Computational fluid dynamics (CFD) is widely used to predict these indices noninvasively.MethodIn this study, uncertainty quantification and sensitivity analysis are performed for the computational prediction of WSS and FFR directly from 3D–0D coupled CFD simulations on idealized stenotic coronary models. Five geometric parameters (proximal, mid, and distal lengths of stenosis; reference lumen diameter; and stenosis severity) and two physiological parameters (mean aortic pressure and microcirculation resistance) are considered as uncertain input variables.ResultsWhen employing the true values of stenosis severity and mean aortic pressure, a discernible reduction of 25% and 9.5% in the uncertainty of the computed proximal WSS, respectively. In addition, degree of stenosis, reference lumen diameter, and coronary resistance contributed the uncertainty of computed FFR, accounting for 41.2%, 31.9%, and 24.6%, respectively.ConclusionThis study demonstrated that accurate measurement of the degree of stenosis and mean aortic pressure is crucial for improving the computational prediction of WSS. In contrast, the reference lumen diameter, degree of stenosis, and coronary resistance are the most impactful parameters for FFR.
Molecular characterization of novel and rare DNA variants in patients with galactosemia
Authors: Maroulis Vasileios , Agathangelidis Andreas , Skouma Anastasia , Sdogou Triantafyllia , Papadakis Manoussos N. , Papakonstantinou Evangelos , Girginoudis Panagiotis , Vorgias Constantinos E. , Aleporou Vassiliki , Kollia Panagoula 
Published: November 2023

Introduction: Galactosemia is an inherited disorder caused by mutations in the three genes that encode enzymes implicated in galactose catabolism. Currently, the only available treatment for galactosemia is life-long dietary restriction of galactose/lactose, and despite treatment, it might result in long-term complications.Methods: Here, we present five cases of newborn patients with elevated galactose levels, identified in the context of the newborn screening program. Genetic analysis concerned a next generation sequencing (NGS) methodology covering the exons and adjacent splice regions of the GALT, GALK1, and GALE genes.Results: Our approach led to the identification of eight rare nonsynonymous DNA variants. Four of these variants, namely, p.Arg204Gln and p.Met298Ile in GALT, p.Arg68Leu in GALK1, and p.Ala180Thr in GALE, were already recorded in relevant databases, yet their clinical significance is uncertain. The other four variants, namely, p.Phe245Leu in GALT, p.Gly193Glu in GALK1, and p.Ile266Leu and p.Ala216Thr in the GALE gene, were novel. In silico analysis of the possible effect of these variants in terms of protein function and stability was performed using a series of bioinformatics tools, followed by visualization of the substituted amino acids within the protein molecule. The analysis revealed a deleterious and/or destabilizing effect for all the variants, supported by multiple tools in each case.Discussion: These results, given the extreme rarity of the variants and the specific phenotype of the respective cases, support a pathogenic effect for each individual variant. Altogether, our study shows that targeted NGS methodologies may offer a time- and cost-effective approach for the genetic investigation of galactosemia and can assist in elucidating the complex genetic background of this disorder.
Machine learning-based integrated identification of predictive combined diagnostic biomarkers for endometriosis
Authors: Zhang Haolong , Zhang Haoling , Yang Huadi , Shuid Ahmad Naqib , Sandai Doblin , Chen Xingbei 
Published: November 2023

Background: Endometriosis (EM) is a common gynecological condition in women of reproductive age, with diverse causes and a not yet fully understood pathogenesis. Traditional diagnostics rely on single diagnostic biomarkers and does not integrate a variety of different biomarkers. This study introduces multiple machine learning techniques, enhancing the accuracy of predictive models. A novel diagnostic approach that combines various biomarkers provides a new clinical perspective for improving the diagnostic efficiency of endometriosis, holding significant potential for clinical application.Methods: In this study, GSE51981 was used as a test set, and 11 machine learning algorithms (Lasso, Stepglm, glmBoost, Support Vector Machine, Ridge, Enet, plsRglm, Random Forest, LDA, XGBoost, and NaiveBayes) were employed to construct 113 predictive models for endometriosis. The optimal model was determined based on the AUC values derived from various algorithms. These genes were then evaluated using nine machine learning algorithms (Random Forest, SVM, Gradient Boosting Machine, LASSO, XGB, NNET, Generalized Linear Model, KNN, and Decision Tree) to assess significance scores and identify diagnostic genes for each algorithm. The diagnostic value of these genes was further validated in external datasets from GSE7305, GSE11691, and GSE120103.Results: Analysis of the GSE51981 dataset revealed 62 DEGs. The Stepglm [Both] and plsRglm algorithms identified 30 genes with the most potential using the AUC evaluation. Subsequently, nine machine learning algorithms were applied to select diagnostic genes, leading to the identification of five key diagnostic genes using the LASSO algorithm. The ADAT1 gene exhibited the best single-gene predictive performance, with an AUC of 0.785. A combination of genes (FOS, EPHX1, DLGAP5, PCSK5, and ADAT1) achieves an AUC of 0.836 in the test dataset. Moreover, these genes consistently exhibited an AUC exceeding 0.78 in all validation datasets, demonstrating superior predictive performance. Furthermore, correlation analysis with immune infiltration strengthened their predictive value by demonstrating the close relationship of the diagnostic genes with immune infiltrating cells.Conclusion: A combination of biomarkers consisting of FOS, EPHX1, DLGAP5, PCSK5, and ADAT1 can serve as a diagnostic tool for endometriosis, enhancing diagnostic efficiency. The association of these genes with immune infiltrating cells reveals their potential role in the pathogenesis of endometriosis, providing new insights for early detection and treatment.
Metabolic reprogramming involves in transition of activated/resting CD4+ memory T cells and prognosis of gastric cancer
Authors: Sun Yue , Liu Li , Fu Yuanyuan , Liu Yaoyao , Gao Xuan , Xia Xuefeng , Zhu Dajian , Wang Xiaping , Zhou Xin 
Published: November 2023

BackgroundLittle is known on how metabolic reprogramming potentially prompts transition of activated and resting CD4+ memory T cells infiltration in tumor microenvironment of gastric cancer (GC). The study aimed to evaluate their interactions and develop a risk model for predicting prognosis in GC.MethodsExpression profiles were obtained from TCGA and GEO databases. An immunotherapeutic IMvigor210 cohort was also enrolled. CIBERSORT algorithm was used to evaluate the infiltration of immune cells. The ssGSEA method was performed to assess levels of 114 metabolism pathways. Prognosis and correlation analysis were conducted to identify metabolism pathways and genes correlated with activated CD4+ memory T cells ratio (AR) and prognosis. An AR-related metabolism gene (ARMG) risk model was constructed and validated in different cohorts. Flow cytometry was applied to validate the effect of all-trans retinoic acid (ATRA) on CD4+ memory T cells.ResultsSince significantly inverse prognostic value and negative correlation of resting and activated CD4+ memory T cells, high AR level was associated with favorable overall survival (OS) in GC. Meanwhile, 15 metabolism pathways including retinoic acid metabolism pathway were significantly correlated with AR and prognosis. The ARMG risk model could classify GC patients with different outcomes, treatment responses, genomic and immune landscape. The prognostic value of the model was also confirmed in the additional validation, immunotherapy and pan-cancer cohorts. Functional analyses revealed that the ARMG model was positively correlated with pro-tumorigenic pathways. In vitro experiments showed that ATRA could inhibit levels of activated CD4+ memory T cells and AR.ConclusionOur study showed that metabolic reprogramming including retinoic acid metabolism could contribute to transition of activated and resting CD4+ memory T cells, and affect prognosis of GC patients. The ARMG risk model could serve as a new tool for GC patients by accurately predicting prognosis and response to treatment.
An electronically conductive 3D architecture with controlled porosity for LiFePO4 cathodes
Authors: Nguyen Martin , Liang Zhiming , Garman Kaitlin , Wang Yangyang , Gestos Adrian , Mo Michael , Ban Chunmei 
Published: November 2023

Thick LiFePO4 (LFP) cathodes offer a promising solution to increasing the areal capacity and reducing the cost of Li-ion batteries while retaining the qualities intrinsic to LFP, including long cycle lifetimes and thermal stability required for electric vehicles and stationary energy storage applications. However, the primary challenges of thick LFP cathodes are poor rate capability and cycling stability due to LFP’s electronically insulating material property, poor electronic conductivity, and long diffusion length at high electrode thicknesses. Herein, we propose an electrode architecture composed of vertically aligned carbon fibers (CFs) attached to a plasticized current collector (PCC) to promote rate capability, cycle life, and further enhance the safety of thick LFP cathodes. The effectiveness of the CF-PCC architecture is demonstrated by electrochemical analysis with a good areal capacity of 3.5 mA cm-2, excellent cycling stability at C/3, and good rate capability up to 1C. These results are confirmed by investigating the architecture’s impact on ionic diffusivity via electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) compared to the conventional slurry cast LFP cathode.
Effects of acupoints-based TENS combined with tDCS on spasticity and motor function in ischemic stroke with spastic hemiplegia: study protocol for a randomized controlled trial
Authors: Qian Xu , Ma Liang-Xiao , Ma Ling-Hui , Zhang Qin-Yong , Xiu Jing-Yun , Wang Xiu-Yan , Sun Tian-Yi 
Published: November 2023

BackgroundSpastic hemiplegia following ischemic strokes seriously impedes the recovery of motor function posing a vast rehabilitation challenge. As the uncertain effects of recommended conventional treatments such as botulinum toxin injections on active functional improvement and potential adverse effects cannot be bypassed, there is an increasing need in alternative, more effective and safer modalities. Acupoints-based transcutaneous electrical nerve stimulation (Acu-TENS) and transcranial direct current stimulation (tDCS) are effective non-invasive modalities for stroke rehabilitation, particularly showing anti-spastic effect and functional improvements as well. However, the optimal stimulation frequency of Acu-TENS and whether combination of Acu-TENS and tDCS exert synergistic effect remain to be investigated.ObjectiveTo evaluate the effects of Acu-TENS combined with tDCS on spasticity and motor function in ischemic stroke patients with spastic hemiplegia and screen the optimal frequency of Acu-TENS.MethodsA total of 90 post-ischemic stroke patients with spastic hemiplegia will be intervened for 4 weeks and followed up for 4 weeks. They will be randomly assigned to three groups including two observation groups and a standard care control group in a 1:1:1 ratio. All patients will receive standard care and regular rehabilitation accordingly. In addition, the two observation groups will receive 12 sessions of Acu-TENS at 20 Hz or 100 Hz for 30 min combined with 1 mA tDCS for 20 min, three times a week, for 4 weeks. The primary outcome is the change in total modified Ashworth scale (MAS) score from baseline to week 4. Secondary outcomes include changes in surface electromyography (SEMG), Fugl-Meyer Motor Function Scale, Modified Barthel Index (MBI), and 10-meter walk test from baseline to week 4. MAS score will also be measured after 4 weeks of follow-up. Adverse events throughout the study will be recorded.DiscussionThis trial will evaluate, for the first time, the therapeutic potentials and safety of Acu-TENS combined with tDCS on spasticity and motor function in stroke patients. It will provide evidence for frequency-dependent anti-spastic effect of Acu-TENS, and a reference for rated parameter setting of new mixed transcutaneous and transcranial stimulation system for stroke rehabilitation, thereby promoting proactive healthcare consequently.Trial registration:Chinese Clinical Trials Register ChiCTR2200067186.
Causal associations of thyroid function and sudden sensorineural hearing loss: a bidirectional and multivariable Mendelian randomization study
Authors: Chen Jialei , Wu Chao , He Jing , Wu Linsui , Yang Yongkang , Zhong Shixun , Luo Jing 
Published: November 2023

BackgroundObservational studies have indicated a potential association between thyroid dysfunction and the risk of sudden sensorineural hearing loss (SSNHL). However, the precise causal relationship between the two remains uncertain. The objective of our study was to assess the causal influence of thyroid function on SSNHL by employing a bidirectional and multivariable Mendelian randomization (MR) approach.MethodsSingle-nucleotide polymorphisms (SNPs) associated with free thyroid (FT4) and thyroid stimulating hormone (TSH) were selected from the summary data of a large genome-wide association study (GWAS) conducted on European individuals. The summary-level data of SSNHL were also obtained from a GWAS, which included 196,592 participants (1,491 cases and 195,101 controls). The MR analysis primarily utilized the inverse variance weighted (IVW) method, with sensitivity analyses performed using the weighted median, MR-Egger, and MR-PRESSO approaches.ResultsIn the IVW method, an elevated genetically predicted FT4 level was found to effectively reduce the risk of SSNHL (OR = 0.747, 95% CI = 0.565–0.987, P = 0.04). These findings were consistent when conducting multivariate MR analysis, which adjusted for TSH levels (OR = 0.929, 95% CI = 0.867–0.995, P = 0.036). However, genetically predicted TSH levels did not emerge as a risk factor for SSNHL (OR = 1.409, 95% CI = 0.895–1.230, P = 0.547). Furthermore, even after adjusting for FT4 levels in the multivariate MR analysis, no evidence of a direct causal relationship between TSH levels and the risk of SSNHL was observed (OR = 1.011, 95% CI = 0.880–1.161, P = 0.867). The reverse MR analysis showed that there was no evidence of a direct causal relationship between SSNHL and the risk of FT4 level (OR = 1.026, 95% CI = 0.999–1.054, P = 0.056) or TSH level (OR = 1.002, 95% CI = 0.989–1.015, P = 0.702).ConclusionWithin the normal range, genetic variants associated with higher FT4 levels demonstrate a potential protective effect against SSNHL, whereas there is no direct causal relationship between TSH levels and the risk of SSNHL.
Computed tomography perfusion imaging-guided intravenous thrombolysis in acute minor ischemic stroke
Authors: Sartor-Pfeiffer Jennifer , Lingel Mirjam , Stefanou Maria-Ioanna , Krumbholz Markus , Hennersdorf Florian , Ernemann Ulrike , Poli Sven , Feil Katharina , Ziemann Ulf , Mengel Annerose 
Published: November 2023

BackgroundOver 50% of acute ischemic stroke (AIS) patients present with minor neurological deficits, and optimal treatment is still debated. The randomized PRISMS trial did not show beneficial effects of intravenous thrombolysis (IVT) in unselected patients with minor stroke and non-disabling neurological deficits.PurposeThe study aimed to evaluate if AIS patients with minor stroke may benefit from computed-tomography-perfusion (CTP)-guided IVT. The primary endpoint was good functional outcomes, defined as a modified Rankin Scale score of 0–2 at 90 days.MethodsAIS patients with a NIHSS of ≤5 presenting within 4.5 h underwent multimodal CT-imaging including CTP. CTP mismatch was defined as hypoperfusion on CTP with time-to-peak delay &gt;6 s without corresponding hypoperfusion in cerebral blood volume. IVT decision was left to the attending stroke physicians. Patients with large vessel occlusion (LVO) and absolute contraindications to IVT were excluded.ResultsIn total, 267 consecutive patients were included [mean age: 72 ± 14 years, 45.3% female patients, 75.3% received IVT, median NIHSS on admission: 3 (IQR 2, 4)]. CTP mismatch was detected in 41.8% of IVT− treated patients (IVT+) and 28.8% of standard treatment patients (IVT−) (p = 0.06). IVT+ had favorable outcomes at 90 days compared to IVT− (p = 0.006), but no interaction with an existing CTP mismatch was detected (ORadj: 1.676; 95% CI: 0.644–4.364). No symptomatic intracranial hemorrhage according to ECASS-III criteria occurred.ConclusionAlthough selected AIS patients with minor stroke may benefit from IVT, CTP mismatch does not correlate with functional outcomes. No benefit from CTP mismatch in guiding IVT was detected in patients without LVO presenting with minor neurological deficits.
Solids, colloids, and the hydrolysis of tetravalent uranium in chloride media
Authors: Grambow B. , Müller R. , Schild D. , Gaona X. 
Published: November 2023

Understanding of the properties of dissolution and precipitation of Uranium under reducing geochemical conditions is important in radioactive waste management and assessments of natural uranium deposits. The mechanism of forming UO2+y from U(VI) and U(IV) containing aqueous solution (1 M NaCl) and the solubilities of the precipitates were studied under well-controlled reducing conditions as a function of pH, particle size, and supersaturation. The results show that tetramer and colloid formation are critical initial steps. Precipitation is not growth-controlled but appears to be nucleation-controlled, with critical nuclei dimensions of one unit cell of UO2. The precipitates were always crystalline, and amorphous UO2 was not observed.
The values of HER-2 expression in the non-muscle-invasive bladder cancer: a retrospective clinical study
Authors: Wang Shuo , Ji Yongpeng , Liu Yiqiang , Du Peng , Ma Jinchao , Yang Xiao , Yu Ziyi , Yang Yong 
Published: November 2023

PurposeThe purpose of this research is to evaluate the association between HER-2 expression and clinicopathological features in patients with non-muscle-invasive bladder cancer (NMIBC).MethodsBetween 2019 and 2022, 204 patients treated with Transurethral resection of the bladder tumor (TURBT) were included in this study. Data of pathologic T (pT) stage, grades of the tumor, age, sex, tumor size and number of the tumors were collected and compared according to the expression level of the human epidermal growth factor 2 (HER-2). ROC curve analysis was performed to assess the discriminative ability of HER-2 expression for tumors grades and pT stage. Multivariable logistic regression analysis were used to evaluate the association between HER-2 expression and tumor grades and pT stage.ResultsPatients were divided into low grade (110, 53.9%) and high grade groups (94, 46.1%) according to the tumor grade. Pathologic stage consisted of pTa in 166 (81.4%) and pT1 in 38 (18.6%). HER-2 expression was semi quantitatively scored to 0 in 44 (21.6%), 1 in 58 (28.4%), 2 in 91 (44.6%), and 3 in 11 (5.4%) cases. HER-2 expression was significantly associated with tumor stages and histological grades, but not with sex, tumor size or number of tumors. The AUC for combination of HER-2 expression with tumor stages and histological grades was 0.652 (p &lt; 0.003) and 0.727 (p &lt; 0.001), respectively.ConclusionThis study demonstrated that HER-2 expression is associated with tumor stages and histological grades in NMIBC. It has diagnostic value for cystoscopic biopsy.
Factors influencing the diagnostic and prognostic values of circulating tumor cells in breast cancer: a meta-analysis of 8,935 patients
Authors: Zhao Hongfang , Wang Luxuan , Fang Chuan , Li Chunhui , Zhang Lijian 
Published: November 2023

BackgroundCirculating tumor cells (CTCs) could serve as a predictive biomarker in breast cancer (BC). Due to its high heterogeneity, the diagnostic and prognostic values of CTC are challenging.MethodsWe searched published studies from the databases of PubMed, Cochrane Library, Embase, and MEDLINE. The detection capability and hazard ratios (HRs) of CTCs were extracted as the clinical diagnosis and prognosis evaluation. Subgroup analyses were divided according to the detection methods, continents, treatment periods, therapeutic plans, and cancer stages.ResultsIn this study, 35 publications had been retrieved with 8,935 patients enrolled. The diagnostic efficacy of CTC detection has 74% sensitivity and 98% specificity. The positive CTC detection (CTC+) would predict worse OS and PFS/DFS in both mid-therapy and post-therapy (HROS, 3.09; 95% CI, 2.17–4.39; HRPFS/DFS, 2.06; 95% CI, 1.72–2.47). Moreover, CTC+ indicated poor survival irrespective of the treatment phases and sampling times (HROS, 2.43; 95% CI, 1.85–3.19; HRPFS/DFS, 1.82; 95% CI, 1.66–1.99). The CTC+ was associated with poor survival regardless of the continents of patients (HROS = 2.43; 95% CI, 1.85–3.19).ConclusionOur study suggested that CTC+ was associated with a worse OS and PFS/DFS in the Asian population. The detection method, the threshold level of CTC+, therapeutic approaches, and sampling times would not affect its diagnostic and prognostic values.
Simultaneous occurrence of two distinct histotypes of ovarian endometriosis-associated cancer in bilateral ovaries: implications for monoclonal histogenesis from a case report
Authors: Zhao Luyang , Liu Yunyue , Liu Feng , Jin Xiangshu , Xu Jia , Zhou Shuting , Meng Yuanguang , Liu Aijun , Yang Weng 
Published: November 2023

BackgroundTransformation of endometriosis to malignancy is a rare occurrence. Clear cell ovarian cancer and endometrioid ovarian cancer are the two histotypes most consistently linked to endometriosis. The exact pathways leading to malignant transformation of endometriosis remain elusive.Case presentationA 41-year-old woman presented to our hospital with a ten days history of abdominal pain which was not responsive to medication. Pathological examination revealed an unexpected finding of bilateral endometriosis associated with distinct malignancies: a clear cell carcinoma in the right ovary and a well-differentiated endometrioid carcinoma in the left ovary. Molecular analysis indicated a shared somatic driver mutation in ING1 in the eutopic endometrium and the bilateral ovaries while simultaneously exhibiting specific genetic alterations unique to each carcinoma. Notably, several common mutation sites were also identified, including previously reported common oncogenes (KRAS, PIK3CA, ARID1A). This finding prompts the hypothesis of a possible monoclonal origin of the two tumours.ConclusionThis case represents an exceedingly rare occurrence of two different histotypes of ovarian endometriosis-associated cancer manifesting simultaneously in bilateral ovaries. Based on genetic analysis, we hypothesize that these malignancies may have a monoclonal origin, providing insights into understanding the different biological mechanisms underlying carcinogenesis.