bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deep learning approach for automated diagnosis of pulmonary embolism on computed tomographic pulmonary angiography
Authors: Ajmera Pranav , Kharat Amit , Seth Jitesh , Rathi Snehal , Pant Richa , Gawali Manish , Kulkarni Viraj , Maramraju Ragamayi , Kedia Isha , Botchu Rajesh , Khaladkar Sanjay 
Published: August 2022

Abstract
Background
Computed tomographic pulmonary angiography (CTPA) is the diagnostic standard for confirming Pulmonary Embolism (PE). Since PE is a life-threatening condition, early diagnosis and treatment are critical to avoid PE-associated morbidity and mortality. However, the diagnosis of PE remains subject to misdiagnosis.
Methods
We retrospectively identified 251 CTPAs performed at a tertiary care hospital between January 2018 to January 2021. The scans were classified as positive (n = 55) and negative (n = 196) for PE based on the annotations made by board-certified radiologists. A fully anonymized CT slice served as input for detection of PE by the 2D segmentation model comprising U-Net architecture with Xception encoder. The diagnostic performance of the model was calculated at both the scan and the slice levels.
Results
The model correctly identified 44 out of 55 scans as positive for PE and 146 out of 196 scans as negative for PE with a sensitivity of 0.80 [95% CI: 0.68, 0.89], a specificity of 0.74 [95% CI: 0.68, 0.80], and an accuracy of 0.76 [95% CI: 0.70, 0.81]. On slice level, 4817 out of 5183 slices were marked as positive for the presence of emboli with a specificity of 0.89 [95% CI: 0.88, 0.89], a sensitivity of 0.93 [95% CI: 0.92, 0.94], and an accuracy of 0.89 [95% CI: 0.887, 0.890]. The model also achieved an AUROC of 0.85 [0.78, 0.90] and 0.94 [0.936, 0.941] at scan level and slice level, respectively for the detection of PE.
Conclusion
The development of an AI model and its use for the identification of pulmonary embolism will support healthcare workers by reducing the rate of missed findings and minimizing the time required to screen the scans.
RETRACTED: Quality testing of mifepristone and misoprostol in 11 countries
Authors: Bower Jason , Chinery Lester , Fleurent Alessandra , Gülmezoglu A. Metin , Im-Amornphong Wallada , Kilfedder Catherine , Procter Petra , Tomazzini Alessandra 
Published: August 2022

Abstract
The authors have requested that this preprint be removed from Research Square.
Construction of a prognostic model for hepatocellular carcinoma patients through bioinformatics analysis
Authors: Jia Jun , Li Dong , Zhang Dan , Cai Jiao , Li Fu , Duan Xue-zhang 
Published: August 2022

Abstract
Backgrounds: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Obesity is closely related to the incidence of various malignant tumors. However, the impact of obesity on tumor prognosis varies with tumor type. Our study used bioinformatics analysis to explore whether body mass index (BMI)-related genes influence the prognosis of hepatocellular carcinoma patients and its potential mechanism. Materials and Methods: We obtained HCC expression data from The Cancer Genome Atlas (TCGA) database and performed Least absolute shrinkage selection operator (LASSO) regression analysis to construct a prognostic model. The International Cancer Genome Consortium (ICGC)-HCC data were used as an independent validation dataset. Results: The prognosis of HCC patients with high BMI was significantly better than that of HCC patients with low BMI. We constructed a prognostic model composed of four genes (-0.092733248*ANXA10-0.168489516*CAPN3-0.204693987*PPP1R32 + 0.097937712*ZNF239) through LASSO regression analysis, which was performed on 101 significantly differentially expressed coding proteins between high- and low-BMI patients. Conclusion: We constructed a prognostic model for HCC patients using integrated bioinformatics analysis and identified four biomarkers that may be used as new therapeutic targets.
Vibrio cholerae circulating throughout a mass vaccination campaign in the Forcibly Displaced Myanmar National population in Cox’s Bazar, Bangladesh
Authors: Taylor-Brown Alyce , Afrad Mokibul , Khan Ashraful Islam , Lassalle Florent , Islam Md. Taufiqul , Tanvir Nabid Anjum , Thomson Nick , Qadri Firdausi 
Published: August 2022

Abstract
Over the last decade, the influx of Forcibly Displaced Myanmar Nationals (FDMNs) into Bangladesh has increased the population of Cox’s Bazar. Due to the already high population density coupled with poor living conditions, FDMNs and the host population of Bangladeshi Nationals (BGDNs) were at heightened risk of diarrhoeal disease outbreaks. Due to this, a nationwide sentinel surveillance programme was established, which revealed that there were seasonal localised sporadic cholera outbreaks in Cox’s Bazar. In this study, we aimed to infer the epidemic risk of the Vibrio cholerae strains circulating in the FDMN and BGDN populations, by determining if isolates linked to the current cholera pandemic were responsible for these outbreaks. Further, to better understand the dynamics of cholera before and during the mass oral cholera vaccination campaign conducted in Cox’s Bazar – the largest in the last decades – we also wanted to understand the links between these circulating strains and the current radiation of lineages causing disease in Haiti and Yemen – places in which reactive vaccination campaigns were conducted in response to outbreaks following humanitarian crises. To do this, we sequenced 223 V. cholerae isolates obtained from stool collected from ten intra-district surveillance sites in Cox’s Bazar, sampling both the FDMN and BGDN subpopulations over a period spanning the pre-and post-vaccination campaign (2014–2019). Phylogenetic analysis of these genomes showed that all isolates belonged to the epidemic “7PET” lineage – responsible for the current cholera pandemic – branching alongside V. cholerae that were circulating in Dhaka and Kolkata between 2014 and 2018. Two distinct sublineages of V. cholerae were present in Cox’s Bazar during the study period; one lineage (PG 1.3) that had radiated globally, and another lineage (PG 1.5) that was restricted to Asia and the Middle East. PG 1.3 was associated with a shorter duration of diarrhoea and lower relative risk of rice watery stool compared to PG 1.5. Given the nature and diversity of the V. cholerae isolated from the BGDN and FDMN subpopulations in Cox’s Bazar, without a vaccine intervention, the risk of local or widespread epidemics or even a pandemic was very high.
Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke
Authors: Chen Jian-Min , Li Xiao-Lu , Chen Qing-Fa , Yang Ye , Xu Sen-Ming , Xu Jianwen 
Published: August 2022

Abstract

Object Through the construction of a competing endogenous RNA (ceRNA) network, this study aimed to search for and investigate the possible molecular mechanisms of potential biomarkers associated with ischemic stroke (IS). Method Seven expression profiles of miRNA, mRNA, and lncRNA were downloaded from the NCBI GEO database. Following the exploration of the differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs), the lncRNA–miRNA and miRNA–mRNA pairs were predicted with target prediction tools, and a ceRNA network was constructed. Subsequently, functional enrichment analyses were performed, a protein–protein interaction (PPI) network was constructed, and the immune cell infiltration landscapes were evaluated using the CIBERSORT algorithm. Finally, we identified the key lncRNAs, miRNAs, and mRNAs of IS using bioinformatics methods and assessed their diagnostic efficacy in the validation datasets. The expression of these key genes was also validated using the quantitative real-time polymerase chain reaction (qRT-PCR) in PC12 cells. Results We constructed the ceRNA network for IS. The DEmRNAs were mainly enriched in inflammatory signaling pathways through enrichment analysis. In the cerebral infarction group, the B cells naïve, T cells naïve, and monocytes had statistically different numbers compared with the control group. We used the criterion AUC > 0.7 to screen key miRNAs, mRNAs, and lncRNA. Finally, six key RNAs were identified. The verification results of the relative RNA expression by qRT-PCR were consistent with the results of the bioinformatics analysis. Conclusion Our results suggest that the ceRNA network exerted an important role in the inflammatory pathogenesis of IS and provided a new strategy to conduct IS research.
BETi enhance ATGL expression and its lipase activity to exert their antitumoral effects in triple-negative breast cancer (TNBC).
Authors: Rossi Teresa , Zamponi Raffaella , Chirico Mattea , Pisanu Maria Elena , Iorio Egidio , Torricelli Federica , Gugnoni Mila , Ciarrocchi Alessia , Pistoni Mariaelena 
Published: August 2022

Abstract
Background
Triple-Negative Breast Cancer (TNBC) is a subtype of breast cancer that differs from other types of invasive breast cancers in the faster spread and worse outcome and it presents limited treatment options. Bromodomain and extra-terminal domain (BET) family proteins are epigenetic readers that control the expression of different oncogenic proteins. BET inhibitors (BETi) are drugs that obstruct BET proteins’ function and are considered a promising anti-cancer strategy. Recent evidence also demonstrated that BET proteins exert their function in regulating metabolic processes.
Methods
RNA-sequencing analysis in TNBC cell lines showed differentially express genes involved in lipid metabolisms after BETi treatment. We mimicked ATGL activity with the short-chain fatty acid (FA) propionate and assessed ATGL function by the ATGL knockdown (KD) in TNBC cell lines. We evaluated ATGL KD effects by analyzing proliferation, the expression of several metabolic genes, lipolysis, mitochondrial function, and metabolic activity in the presence or absence of BETi. Chromatin Immunoprecipitation identified FoxO1 binding to the PNPLA2 promoter.
Results
Treatment of TNBC cells with two BETi markedly increased ATGL expression and lipolytic function, decreasing intracellular lipid content in the dose and time-dependent. The intracellular composition of FAs after BETi treatment reflected a significant reduction in neutral lipids. We confirmed the dependency of TNBC on FAs by mimicking ATGL activity with the short-chain FA propionate. We established that ATGL KD decreased ROS, upregulated SOD1 level, and reduced CPT1a. ATGL KD helps to switch from mitochondrial ß-oxidation to a glycolytic phenotype as their expression analysis revealed an upregulation of glycolytic markers and downregulation of ß-oxidation genes. The enhanced glycolysis reflected a marked increase in the mitochondrial metabolic activity measured by the MTT assay. Finally, we found FoxO1 upregulated upon JQ1 treatment. We established that FoxO1 binds the PNPLA2 promoter only after BETi usage and FoxO1 overexpression leads to ATGL induction. However, FoxO1 only partially prompted the induction of ATGL expression by BETi.
Conclusions
Although the anti-proliferative effects achieved by BETi are not dependent on ATGL mediating lipolysis, the results of this study showed that BETi promoted their antitumoral effects by altering mitochondrial dynamics through ATGL
CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis
Authors: Fu Wen , Wang Xianxing , Xiang Jifeng , Chen Shengkai , Xia Renpei , Qin Fanbo , Li Zhuo , Wang Huaizhi , Xie Chuanming , Liu Changjiang 
Published: August 2022

Abstract
Background
Growing evidence suggests that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear.
Methods
CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft models were constructed for in vivo experiments.
Results
CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promots the progression of PDAC.
Conclusions
This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.
Effects of repetitive twice-weekly tDCS stimulations on fatigue and fatigability in people with multiple sclerosis
Authors: Linnhoff Stefanie , Haghikia Aiden , Zaehle Tino 
Published: August 2022

Abstract
Fatigue is associated with a dramatically decreased quality of life in people with multiple sclerosis (pwMS). It refers to a constant subjective feeling of exhaustion and a performance decline, known as fatigability. However, inconsistency and heterogeneity in defining and assessing fatigue have led to limited advances in understanding and treating MS-associated fatigue. Transcranial direct current stimulation (tDCS) has emerged as a promising, non-pharmaceutical treatment strategy for subjective fatigue. However, whether repetitive tDCS also have long-term effects on time-on-task performance has not yet been investigated. Thus, this pseudorandomized, single-blinded, and sham-controlled study aimed to investigate tDCS effects on behavioral and electrophysiological parameters. PwMS received eight twice-weekly 30-minute tDCS stimulations over the left dorsolateral prefrontal cortex. Fatigability was operationalized as time-on-task-related changes in reaction time variability and P300 amplitude. Additionally, subjective trait and state fatigue ratings were assessed. The results revealed a significant tDCS effect on subjective trait fatigue ratings that lasted at least four weeks after the stimulations. However, the ratings declined after both anodal and sham tDCS. No effects were found on subjective state fatigue and objective fatigability parameters. Linear Mixed Models and Bayesian Regression models likewise favored the absence of a tDCS effect on fatigability parameters. Our results confirm the complex relationship between MS-associated fatigue and fatigability. Reliable and clinically relevant parameters need to be established to extend the potential of tDCS for treating fatigability. Furthermore, our results indicate that consecutive stimulations rather than twice-weekly stimulations should be the preferred stimulation scheme in future studies.
Enhanced pain facilitation rather than impaired pain inhibition in burning mouth syndrome female patients
Authors: Gremeau-Richard Christelle , Pionchon Paul , Mulliez Aurélien , Dualé Christian , Dallel Radhouane 
Published: August 2022

Abstract
Background
Deficient endogenous pain modulation has been implicated in the development and exacerbation of chronic orofacial pain. To date, relatively little is known regarding the function of the endogenous pain modulation in patients with burning mouth syndrome (BMS). This case-control study investigated endogenous pain modulation in women with BMS.
Methods
Conditioned pain modulation (CPM) was assessed upon temporal summation (TSP) of thermal pain. Forty female subjects, 20 BMS patients and 20 age-matched control subjects, were included in a 2 session-protocol. Mechanical and thermal pain thresholds were measured on the forearm and hand. TSP was obtained using repetitive laser-evoked thermal stimuli applied on the non-dominant hand, at an intensity yielding to moderate pain. During TSP, CPM was produced by immersing the contralateral foot in a water bath at painful cold (8°C) temperature. In control conditions, the foot was immersed in a water bath at not painful (30°C) temperature.
Results
BMS was not associated with any impairment in thermal as well as mechanical extracephalic pain thresholds. TSP and CPM efficacy were similar in BMS patients and control subjects. However, BMS patients exhibited enhanced extracephalic heat hyperalgesia.
Conclusion
This study reveals that there is no impairment of endogenous pain inhibition mechanisms in BMS patients, but rather an increase in pain facilitation.
Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation
Authors: Karg Elena , Baldow Christoph , Zerjatke Thomas , Clark Richard , Roeder Ingo , Fassoni Artur , Glauche Ingmar 
Published: August 2022

Abstract
Discontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials. Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success. Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI. Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.
The Klotho-FGF23-CPP axis and cardiovascular outcomes in diabetic patients with chronic limb threatening ischemia: a prospective study
Authors: Biscetti Federico , Rando Maria Margherita , Cecchini Andrea Leonardo , Nicolazzi Maria Anna , Angelini Flavia , Iezzi Roberto , Eraso Luis H , Dimuzio Paul J , Pitocco Dario , Gasbarrini Antonio , Massetti Massimo , Flex Andrea 
Published: August 2022

Abstract
Background: Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-FGF23-CPP axis is associated with endothelial injury and cardiovascular risk.The aim of this study was to analyze the relationship between Klotho-FGF23-CPP serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI.Methods: Baseline levels of Klotho, FGF23, and CPP, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER.Results: A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs 446.4 ± 171.7 pg/mL, p<0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs 53.2 ± 15.4 pg/mL, p<0.01) and CPP (461.8 ± 168.6 pg/mL vs 269.3 ± 184.3 pg/mL, p<0.01) were significantly associated with the development of MACE. ROC analysis confirmed the predictive power of the Klotho-FGF23-CPP axis. Furthermore, decreased Klotho serum levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p<0.01).Conclusions: Klotho-FGF23-CPP axis imbalance is a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.
A Novel Optimization Method for Belief Rule Base Expert System with Activation Rate
Authors: Xiang Gang , Wang Jie , Han XiaoXia , Tang Shuaiwen , Hu Guanyu 
Published: August 2022

Abstract
Although the belief rule base (BRB) expert system has many advantages, such as the effective use of semi-quantitative information, objective description of uncertainty, and efficient nonlinear modeling capability, it is always limited by the problem of combinatorial explosion. The main reason is that the optimization of a BRB with many rules will consume many computing resources, which makes it unable to meet the real-time requirements in some complex systems. Another reason is that the optimization process will destroy the interpretability of those parameters that belong to the inadequately activated rules given by experts. To solve these problems, a novel optimization method for BRB is proposed in this paper. Through the activation rate, the rules that have never been activated or inadequately activated are pruned during the optimization process. Furthermore, even if there is a complete data set and all rules are activated, the activation rate can also be used in the parallel optimization process of the BRB expert system, where the training data set is divided into some subprocesses. The proposed method effectively solves the combinatorial explosion problem of BRB and can make full use of quantitative data without destroying the original interpretability provided by experts. Case studies prove the advantages and effectiveness of the proposed method, which greatly expands the application fields of the BRB expert system.
Research on fractional order modeling and PIλ control strategy of CLLC bi-directional resonant converter
Authors: Li Di , Lv Qingquan , Zhang Zhenzhen , Huang Yunfan , Dong Haiying 
Published: August 2022

Abstract
There are problems such as insufficient modeling accuracy of the CLLC bi-directional resonant converter in integer order, failure to accurately describe the actual conditions of the system, poor dynamic performance of classical PI control strategy, and failure of the system to reach the stable state quickly and smoothly. First, based on the fractional order calculus theory, this paper proposes an extended describing function method based on fractional order, establishes the mathematical model of the fractional order and small signal model of the fractional order of the CLLC bi-directional resonant converter, obtains the fractional order transfer function of the system, constructs the PI λ control strategy of the fractional order of the CLLC bi-directional resonant converter, and builds the simulation model of the CLLC bi-directional resonant converter based on Matlab/Simulink software for simulation verification. Finally, a principle prototype was built in the laboratory to verify the correctness and feasibility of the CLLC bi-directional resonant converter of the fractional order and theoretical analysis of the PI λ control strategy of the fractional order.