bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nomograms to Predict Individual Potential Benefit from Targeted Therapy for patients with lymph node positive Luminal B (HER2-) breast cancer
Authors: Yue Yuhan , Meng Ran , Li Dan , Ma Haiyan , Wu Yuruo , Li Pengcheng , Liang Junqing , Wang Xin 
Published: January 2024

Abstract

PurposeTo construct nomograms combining clinicopathological characteristics, bone metastases (BM), viscera metastases (VM) and cancer-related deaths (CRD) to predict the higher-risk patients with lymph node positive (N+) Luminal B (HER2-) breast cancer (BC).MethodKaplan-Meier survival analysis, Venn diagram, Bar charts were used to describe the data for subsequent metastasis and CRD. Thirty-six clinicopathological characteristics were extracted in univariate and multivariate Cox regression analyses to develop nomogram to predict potential risk of BM, VM and CRD among patients with N+ Luminal B (HER2-) BC. The calibration plots, concordance index and receiver operating characteristics (ROC) analysis were applied to determine the nomogram accuracy.ResultThe median age of 8139 patients was 51 years, with a median follow-up of 124 months (4–216 months). There was no statistical difference between the metachronous primary bilateral BC and synchronous primary bilateral BC. The number-peak period of patients with subsequent BM was the third year, VM was the 4th year and CRD was the 6thyear (range second–6th year, 4th–6th year and third–8th year, respectively). BM, VM and CRD nomograms showed outstanding performance and discriminative ability (C-index 0.69, 0.68 and 0.71, respectively). The calibration curves and ROC curves analysis demonstrated the considerable clinical usefulness of the combined nomogram. Three clinical examples showed results differences in optimal period who had similar pathological stage.ConclusionThe developed nomogram model consisting of time-event-dependent clinicopathological characteristics could reliable in predicting BM, VM and CRD probability of patients with N+ Luminal B (HER2-) BC.
Modification of Ki67 on Prognostic Model of Extranodal NK/T Cell Lymphoma
Authors: Wu ShiShou , Zhang Wenfeng , Song Liling , Jiang Lei , Yang Ping , An Licai , Zhang Yuanfeng , Wang Yunjun , Gao Yuan , Liu Yifei , Zhang Jiandi , Yu Guohua , Pan Yu 
Published: January 2024

Abstract
Background: To explore the value of Ki67 in the prognostic evaluation of extranodal NK / T cell lymphoma and the modification effect of NK cell lymphoma prognostic risk index (PINK) and Nomogram modified risk index (NRI).
Methods: A retrospective analysis of the clinical data of 106 patients with extranodal nasal NK/T cell lymphoma diagnosed in Yantai Yuhuangding Hospital and the affiliated Hospital of Nantong University from 2008 to 2020. Ki67 immunohistochemical staining and Quantitative Dot Blot (QDB) which is an absolute protein quantitative detection were performed on pathological paraffin specimens, and the R4.1.0 and SPSS were used to analyze the data and determine the threshold.
Results: A total of 106 patients,75/106 (70.7%) patients were male and 31/106(29.3%) were female. The onset age of patients ranged from 14 to 86 years old, and the median onset age was 60 years old. As of September 10, 2020, 105 patients were followed up, 54/105(51.4%) patients were died, 51/105 (48.6%) patients were survived, and the median survival time was 330 days. Immunohistochemical results showed that patients with Ki67 proliferation index > 60% or MIB1 (Ki67) > 11.9 nmol/g had worse prognosis. The data were modified by Ki67 (IHC) and Ki67 (QDB), and the survival analysis of PINK and NRI models showed that there were statistically significant differences among the risk groups (P < 0.001). Compared with Ki67 (IHC), Ki67 (QDB) modified PINK and NRI models could significantly improve their predictive ability (AUCPINK, 0.67 vs 0.74; C-indexPINK, 0.68 vs 0.75; AUCNRI, 0.74 vs 0.80; C-indexNRI, 0.69 vs 0.71).
Conclusions: The results of Ki67 by QDB could significantly enhance the predictive ability of PINK and NRI models. PINK model modified by Ki67 QDB can more accurately describe the prognosis of ENKTCL patients. The absolute quantitative detection technology of QDB protein is expected to be applied to clinical laboratory detection to achieve individualized and accurate diagnosis and treatment of tumors.
A New Prognostic Nomogram for Extranodal NK/T cell lymphoma Based on Clinical and Pathological Parameters
Authors: Wu ShiShou , Liu Yifei , Jiang Lei , An Licai , Zhang Yuanfeng , Gao Yuan , Wang Yunjun , Li Na , Yu Guohua 
Published: January 2024

Abstract

Objects: To establish a risk hierarchical model to evaluating the prognostic of ENKTCL based on the clinical and pathological parameters.
Methods: 1.Based on the prognostic analysis of IHC and QDB results, the prognostic model was established (NK/T cell lymphoma International prognostic Index，NIPI). 2. The data was analyzed by R.4.1.0 and the threshold was determined. AUC was used to compare with other prognostic risk models of extranodal NK/T cell lymphoma.
Results: 1. NIPI based on age, MTP53, Ki67, LDH, hemoglobin and lymphocyte/platelet ratio was divided all patients into four groups with different prognostic risk. There was significant difference among different groups by NIPI(IHC) (P<0.001)and the AUC was 0.72. There was no significant difference in prognosis by Ann Arbor stage. There were significant differences in prognosis among different prognostic model groups（PIPI=0.00036、PPINK＝0.00017、PNRI＜0.001）. There was significant difference among the four groups by NIPI(QDB) (P＝0.00014) and the AUC was 0.800.
Conclusion: 1. NIPI can predict the prognostic risk of ENKTCL patients and can help to achieve individual accurate diagnosis and treatment. 2. QDB analysis has more prominent advantages in accurate diagnosis and treatment, and it is expected to become an important experimental technique for clinical laboratory detection.
STIM1/Orai1-mediated Ca 2+ influx contributes to the ASM phenotype modulation and ASM-related ECM deposition in asthma
Authors: Ni Hangqi , Li Ting , Chen Junjun , Wei Yuying , Xia Mengling , Wang Qing 
Published: January 2024

Abstract
Background: Phenotype modulation of airway smooth muscle cells (ASMC), defined as a more proliferative/synthetic type switched from contractile cells, plays an important role in airway remodeling of asthma. STIM1 and Orai1, the key aspects mediating store-operated Ca2+ entry (SOCE), have been shown to promote ASMC proliferation and migration. In this study, we explored the role of STIM1/Orai1-mediated SOCE in ASMC phenotype transition, and further investigated their involvement in the extracellular matrix (ECM) deposition in asthma.
Methods: The ASMCs from C57BL/6 mice were prepared and incubated with PDGF-BB to induced the phenotype switching. SKF-96365, an inhibitor of STIM1/Orai1, was used to detect the effect of SOCE in the ASMC phenotype transition and ASMC-related ECM doposition. Cell counting kit-8 assay, immunocytochemistry staining, enzyme-linked immunosorbent assay, and western blot assay were employed to detect the ASMC’s proliferation and the expressions of contractile proteins, inflammatory cytokines as well as exacellular matrix. Moreover, we prepared the asthmatic mice model with SKF-96365 intranasal or intratracheal instillation and western blot assay were employed to determine the effect of SOCE repression in ECM deposition in vivo.
Results: We prepared the “proliferative/synthetic” type ASMCs with PDGF-BB treatment. and detected the increased expressions of STIM1 and Orai1 in phenotype switched ASMCs, accompanied by an enhance of SOCE. SKF-96365 could obviously block the activation of SOCE in ASMC. Meanwhile, the addition of SKF-96365 in phenotype switched ASMCs could significantly attenuate their increased proliferation ability, inflammatory cytokines secretion, and decreased contractile proteins contents induced by PDGF-BB. Moreover, we detected that PDGF-BB-induced “proliferative/synthetic” ASMCs can produce more ECM components, including collagen I, elastin and fibronectin, and metalloproteinases (MMPs) such as MMP2 and MMP9, which could be inhibited by the STIM1/Orai1 blocker SKF-96365. In vivo experiments also showed the similar results that SKF-96365 reduced the ECM deposition and MMPs production in the asthmatic mice model.
Conclusion: These observations demonstrated the prominent role of STIM1/Orai1-mediated SOCE in the phenotype modulation of ASMCs and their influence in the ASMC-induced excessive and altered ECM deposition. Therefore, our results indicated that STIM1/Orai1-mediated SOCE may take part in the airway remodeling of asthma.
Synthesis of novel biphenyls containing thiophene, pyridazinimine and 1,3,4-thiadiazole moieties, and their effects on the mortality, oxidative stress and antioxidant enzymes in the desert locust, Schistocerca gregaria (Forskål) (Orthoptera: Acridiidae)
Authors: Eldebss Taha M. A. , Shaurub El-Sayed H. , Mekky Ahmed E. M. , Shaaban Mohamed R. , Farag Ahmad M. 
Published: January 2024

Abstract
Biphenyls acting on insects are an intensive research area now. In order to search for novel biphenyl candidates, a series of biphenyl derivatives containing thiophene, pyridazinimine and 1,3,4-thiadiazole moieties were synthesized. Their insecticidal activities on the newly molted fifth nymphal instars of the desert locust, Schistocerca gregaria, were screened. Additionally, the effect of the most toxic compound on the level of malondialdehyde (MDA) and on the activity of the antioxidant enzymes, catalase (CAT) and glutathione S-transferase (GST), in the thoracic muscles and the midgut was also evaluated. The synthesized compounds were characterized through 1HNMR, 13C NMR and high-resolution mass spectrometry. Bioassay indicated that they showed insecticidal activity; the compound 11 with thiophene nucleus (8-13), phenylamino group and ethyl carboxylate moiety, in a certain arrangement, in addition to biphenylcarbonyl was the most toxic one, with LC50 of 42.90 ppm using leaf – dip technique. This compound increased the activity of MDA and GST, whereas the activity of CAT decreased. The present work demonstrated that biphenyl derivatives can be used as possible major compounds to develop novel insecticides. Additionally, antioxidant biomarkers such as MDA and GST and CAT were involved in the free radical scavenging in response to exposure of S. gregaria to the target compound 11.
A Model Transformation Method Based on Simulink/Stateflow for Validation of UML Statechart Diagram
Authors: Wu Runfang , Du Ye , Li Meihong 
Published: January 2024

Abstract

A model extraction and transformation method based on state refinement and semantic mapping is proposed to address the challenges of modeling difficulty and resource consumption in the symbol verification process of software requirement modeling. Considering the characteristics of UML state diagrams, a semantic extraction approach from the statechart diagram to the validation model is proposed in this paper. The mapping of various elements from the state diagram to the validation model was defined in a rule-based manner, composite states were refined to reduce the hierarchical structure, and the effectiveness of the mapping was evaluated. Then, a semantic algorithm based on mapping rules was designed, and model transformation was achieved through a specific feedback process for railway turnout control. Finally, the protocol was detected using the NuSMV validation tool, and faults were injected to validate the transformed validation model. The results indicate that the algorithm has good accuracy and practicality.
Association between systemic immune inflammation index and osteoarthritis in US adults: a cross-sectional study
Authors: Fang Jianguo , Liu Cai , Wang Duojun , Zhang Hui , Xu Xin , Lin Zaijun 
Published: January 2024

Abstract
Background
The relationship between systemic immune inflammation index (SII) and the osteoarthritis (OA) has not been well established. This study aimed to investigate the associations between SII and OA risk using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2016.
Methods
A cross-sectional study was conducted using data from participants in NHANES 2005–2016. SII is calculated as platelet count × neutrophil count/lymphocyte count. Multivariable logistic regression models were used to explore the link between SII and osteoporosis, adjusting for potential confounders.
Results
A total of 18,459 participants were included, of which 1130 reported having OA. After adjusting for potential confounders, an inverse association was observed between SII and OA (OR = 1.27; 95% CI = 1.07–1.51, p = 0.006). Moreover, we also identify that SII of 515.56 is the optimal cut-off value, indicating that when the SII value exceeds the cut-off value, the risk increases rapidly.
Conclusions
In this large, nationally representative sample of U.S. adults, higher SII was negatively associated with the risk of OA. Further prospective studies are needed to confirm these findings and elucidate potential underlying mechanisms.
A novel reinforcement learning-based hybrid intrusion detection system on fog-to-cloud computing
Authors: Najafli Sepide , Haghighat Abolfazl Toroghi , Karasfi Babak 
Published: January 2024

Abstract
The increasing growth of the Internet of Things and its open and shared character has led to a rise in new attacks exponentially. As a consequence, the quick detection of attacks in IoT environments is essential. The intrusion detection system (IDS) is responsible for protecting and detecting the type of attacks. Creating an IDS that works in real-time and adapts to environmental changes is critical. In this paper, we propose a deep reinforcement learning-based (DRL) adaptive IDS that addresses the mentioned challenges. DRL-based IDS helps to create a decision agent, who controls the interaction with the indeterminate environment and performs binary detection (normal/intrusion) in fog. For multi-class classification of attacks, we use the ensemble method in the cloud. The proposed approach is evaluated on the CICIDS2018 dataset, in binary and multiclass classification. The results show that the proposed model achieves a comparable performance in detecting intrusions and identifying attacks and it reduces the prediction time significantly. Furthermore, it is a suitable solution for underrepresented attacks. Overall, combining multiple methods can be a great way for an intrusion detection system.
Effect of Post COVID-19 hypoxia on Placenta of Pregnant Women: A possible Role of Hypoxia Inducible Factor-1α
Authors: Abbas Fatma , Abd-Elaziz Ebtihal A. , Helbawi Fatma M. , Abbas Asmaa , Abd-Elsamea Fatma Sayed , Tohamy Tohamy Anwar , Sobh Ahmed M. A. 
Published: January 2024

Abstract
The hypoxia-inducible factors (HIF) are considered master regulators of oxygen homeostasis and are oxygen level sensitive. Currently, there is no information regarding the expression of HIF-1α in pregnant women with COVID-19 infection and its potential involvement in the placentation of this condition. The current study aims to detect the expression of HIF-1α and possible molecular link between the expression of HIF-1α and PLGF. A case-control study was conducted in a tertiary university hospital between January and September 2022. Placental tissue of post COVID-19 infected pregnant women (n = 34) and healthy control (n = 16) were collected and processed for gene expression of HIF-1α and PLGF by Quantitative real-time PCR. There was statistically significant higher median level of HIF-1α among cases compared to controls (P < 0.001). Moreover, there was a statistically significant higher median level of PLGF among cases compared to controls (P < 0.001). There was statistically significant moderate positive correlation between HIF-1α and PLGF gene (r = 0.636, P < 0.001) among studied samples, however no statistically significant correlation between the two genes among cases and controls groups separately. In conclusion, the higher levels of HIF-1α and PLGF in the placentas of post COVID-infected pregnant women compared to normal pregnant women indicate that COVID-19 hypoxia did not affect the process of placentation. This is confirmed also by the positive correlation between HIF-1α and PIGF in placental tissues among total studied samples.
Causal association of gut microbiota with type 2 diabetes, type 1 diabetes and glycemic traits: a two-sample Mendelian randomization study
Authors: Zhao Jiaoyan , Xing Wenguo , Li Yuqian , Mao Zhenxing , Wang Chongjian , Zhang Shuhua , Li Zhuoyang , Li Yan , Li Jia , Yang Tianyv , Li Linlin 
Published: January 2024

Abstract
Purpose
Growing evidence from observational studies reveals that gut microbiota is associated with type 2 diabetes (T2D), type 1 diabetes (T1D) and glycemic traits. Aiming to comprehensively explore these causal relationships, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis.
Method
We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) summary data. The gut microbiota-related GWAS data were obtained from the MiBioGen consortium, and the summary statistics for T2D and T1D from the GWAS database. Besides, the 3 glycemic traits (2h-glucose, fasting glucose, fasting insulin) summary statistics were all obtained from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). The selection of instrumental variables strictly conformed to a set of predefined inclusion and exclusion criteria. Inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode and simple mode were used to access the causal association. Several sensitivity analyses are used to ensure the robustness of the results.
Results
According to causal effect models with MR analysis, we identified 7 significant causal relationships between gut microbiota and diabetes (T2D/T1D) and glycemic traits, including phylum Verrucomicrobia, genus Actinomyces, family Veillonellaceae, class Melainabacteria, order Gastranaerophilales, family unknownfamily.id.1000001214 and phylum Proteobacteria. Evidence from multiple sensitivity analyses further supports these associations.
Conclusions
Our research revealed that gut microbiota was causally associated with diabetes (T2D/T1D) and glycemic traits and may provide fresh ideas for early detection and treatment.
NFIB controls chemosensitivity in small cell lung cancer by suppressing Notch signaling activity
Authors: Qin Weixin , Wang Ziyan , Deng Shuzhe , Qiu Huilei , Meng Hongxue , Geng Jingshu 
Published: January 2024

Abstract
Background: Small cell lung cancer(SCLC) is a highly aggressive malignant tumor type, characterized by universal acquired therapeutic resistance during rapidly recurrence. However, we have a poor understanding of the mechanisms underlying development of resistance. NFIB is a bona fide oncogene in SCLC with effects on proliferation, invasion, and apoptosis inhibition.
Methods: The expression of NFIB and related genes was evaluated in SCLC cells and tissue specimens, by western blot, RT-PCR immunofluorescence and immunohistochemistry. The relationship between genes was verified by ChIP-PCR experiments. CCK8 assays was used for drug resistance experiments.
Results: NFIB is highly correlated with NE markers and may be participated in the generating of tumor heterogeneity mediated in part by Notch1. The suppressive effect of NFIB on Notch1 is relieved and led to NE gene inhibiting when SCLC cells lack of NFIB. These cells are slow growing and also relatively chemoresistant. Importantly, Notch blockade in combination with chemotherapy alleviates the formation of intratumoral heterogeneity and enhances chemosensitivity.
Conclusions: NFIB can be both tumor-pro-tumorigenic and chemosensitizing in SCLC. NFIB knockdown results in endogenous activation of the Notch pathway. These results uncover the dual character of oncogene as NFIB in SCLC and offer perspectives for efficacious combination therapies that might also hold promise for treating human SCLC.
Comparison of two surveillance criteria for detecting ventilator associated problems in critically- ill patients who have COVID-19
Authors: Güven Damla Karadeniz , Metan Gökhan , Dizman Gülçin Telli , Durhan Gamze , Topeli Arzu , Demir Ahmet Uğur 
Published: January 2024

Abstract
Background
We aimed to compare the effectiveness of traditional Ventilator associated pneumonia (VAP) and Ventilator associated event (VAE) surveillance definitions in the determination of mechanical ventilator related infectious complications in patients who required invasive mechanical ventilation (MV) for COVID-19 associated respiratory insufficiency.
Methods
This study was conducted in the Medical Intensive Care Unit (ICU) of Hacettepe University Hospital in Ankara between July 2020 and June 2021. Seventy-seven COVID-19 patients who required MV more than 48 hours were included. The National Healthcare Safety Network (NHSN) Ventilator associated pneumonia (VAP)/PNEU definition was used for VAP surveillance. NHSN Ventilator-associated event (VAE) criteria were used for VAE surveillance. Kappa analysis was performed to evaluate the concordance between VAP and VAE.
Results
The incidence of VAP was found as 13.55 (95% confidence interval (CI), 9.33–19.03) per 1000 ventilator days and the incidence of VAE was 6.16 (95% CI, 3.44–10.16) per 1000 ventilator days. Infectious Ventilator Associated Complication (IVAC) was detected in 10 (13%) patients, and 4 (5.2%) patients had Possible Ventilator Associated Pneumonia (PVAP). Eleven patients met both VAP and VAE criteria, however, VAP and VAE were detected on the same MV day in only 1 (9%) patient. VAP was detected before VAE in 8 (72%) patients. The concordance between VAP and VAE was low (0.260).
Conclusions
VAP criteria detected higher rate of ventilator associated infections when compared with VAE. There was no correlation between two algorithms. There is a risk of underestimation of ventilator associated infectious complications when using VAE criteria for surveillance.