bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab vs cemiplimab for the treatment of advanced non-small cell lung cancer with PD-L1 expression levels of at least 50%: A network meta-analysis and cost-effectiveness analysis
Authors: Li Yan , Liang Xueyan , Yang Tong , Guo Sitong , Chen Xiaoyu 
Published: September 2022

BackgroundPembrolizumab and cemiplimab have been approved as treatment for advanced non-small-cell lung cancer (NSCLC) with high programmed death ligand-1 (PD-L1) expression. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with that of cemiplimab in the treatment of advanced NSCLC with high PD-L1 expression from a societal perspective in the United States.Materials and methodsCost-effectiveness analysis integration of the network meta-analysis framework was performed using data from the EMPOWER-Lung 1, KEYNOTE 024, and KEYNOTE 042 phase 3 randomized clinical trials. A network meta-analysis including 2289 patients was constructed, and the Markov and partitioned survival (PS) models were used to assess the cost-effectiveness of pembrolizumab compared with that of cemiplimab for the treatment of high PD-L1 expression (≥50% of tumor cells). The time horizon was 10 years. The main outcomes were overall costs, incremental cost-effectiveness ratios (ICERs), quality-adjusted life-years (QALYs), life-years, incremental net health benefits (INHB), and incremental net monetary benefits (INMB). The robustness of the model was verified using one-way and probabilistic sensitivity analyses, and subgroup analyses were conducted.ResultsTreatment of advanced NSCLC with high PD-L1 expression with pembrolizumab achieved 0.093 QALYs and was associated with an incremental cost of $10,657 compared with cemiplimab, yielding an ICER of $114,246/QALY. The ICER in the PS model was similar to that in the Markov model, with a difference of $3,093/QALY. At a willingness-to-pay (WTP) threshold of $100,000/QALY, INHB, and INMB of pembrolizumab were -0.013 QALYs and -$1,329, respectively, and the probability of cemiplimab was 51% when compared with pembrolizumab. When the WTP threshold increased to $150,000/QALY, the INHB and INMB of pembrolizumab were 0.022 QALYs and $3,335, respectively, and the probability of pembrolizumab was 51.85%. One-way sensitivity analysis indicated that the models were sensitive to pembrolizumab and cemiplimab costs. Subgroup analysis revealed that treatment with pembrolizumab was related to a higher INHB in several subgroups, including patients with brain metastases at baseline.ConclusionOur findings suggest that the WTP threshold should be considered when choosing between cemiplimab and pembrolizumab to treat advanced NSCLC with high PD-L1 expression. Reducing the cost of pembrolizumab may lead to valuable outcomes.
The interplay between prenatal liver growth and lung development in congenital diaphragmatic hernia
Authors: Ott Katherine C. , Bi Michael , Scorletti Federico , Ranginwala Saad A. , Marriott William S. , Peiro Jose L. , Kline-Fath Beth M. , Alhajjat Amir M. , Shaaban Aimen F. 
Published: September 2022

ObjectiveLiver herniation is a known risk factor for increased severity in CDH and is associated with clinically significant pulmonary hypoplasia and pulmonary hypertension. Better studies are needed to understand the growth of the herniated liver compared to the liver that remains in the abdomen and how this liver growth then affects lung development. Serial hi-resolution fetal MRI enables characterization of liver growth throughout gestation and examination of macroscopic features that may regulate liver growth. Here, we hypothesized that the nature of liver herniation affects liver growth and, in turn, affects lung growth.MethodsClinical data were retrospectively collected from consecutive cases of prenatally diagnosed isolated left-sided or right-sided CDH from June 2006 to August 2021. Only those cases with MRI lung volumetry for both mid-gestation and late-gestation time points were recruited for analysis. Cases with fetal chromosomal abnormalities and other major structural abnormalities were excluded. Fractional liver volume and liver growth was indexed to estimated fetal weight and compared to lung growth.ResultsData was collected from 28 fetuses with a left liver-down CDH (LLD), 37 left liver-up CDH (LLU) and 9 right liver-up CDH (RLU). Overall, RLU fetuses had greater overall and fractional (intra-thoracic vs. intra-abdominal) liver growth when compared to LLD and LLU fetuses. Additionally, intra-thoracic liver growth was consistently slower than intra-abdominal liver growth for either right- or left-sided CDH. When the liver was not herniated, a positive correlation was seen between liver growth and lung growth. However, when the liver was herniated above the diaphragm, this positive correlation was lost.ConclusionRight-sided CDH fetuses exhibit greater liver growth compared to left-sided CDH. Liver herniation disrupts the normal positive correlation between liver and lung growth that is seen when the liver is entirely within the abdomen.
Investigating the cardioprotective effects of Fuzheng Yangxin recipe based on network pharmacology and experimental evaluation
Authors: Wang Anzhu , Zhao Wei , Yan Kaituo , Guo Lijun , Gao Feng , Chen Jingjing , Wang Yifei , Ma Xiaochang 
Published: September 2022

Background: Under Chinese medicine theory guidance, Fuzheng Yangxin Recipe (FZYX) is clinically effective for the treatment of heart failure (HF) caused by ischemic heart disease (IHD). This study aimed to investigate the mechanism of the myocardial protective effects of FZYX on HF.Materials and methods: The Gene expression omnibus database was used to identify differential genes of the IHD subtype. Through network pharmacological methods, the targets of the active components of FZYX were obtained. We also constructed IHD-induced HF model rats by ligating the left anterior descending coronary artery. Echocardiography, pathological section staining, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry, and quantitative real-time PCR analyses were performed to verify the protective effects of FZYX on the myocardium.Results: We identified 53 active components and 37 potential targets of FZYX associated with the IHD subtype. Signal transducer and activator of transcription 3 (STAT3) is a key protein in the protein-protein interaction (PPI) network. A total of 146 biological processes, 10 cellular components and 40 molecular function subcategories were identified by Gene Ontology (GO) enrichment analysis, and 18 signalling pathways, including apoptosis, were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In vivo experiments showed that FZYX significantly inhibited cardiomyocyte apoptosis, promoted the expression and phosphorylation of STAT3, and improved cardiac function.Conclusion: FZXY improves cardiac function and protects cardiomyocytes from injury via multi-component, multi-target and multi-pathway action, especially its possible role in regulating STAT3 expression and anti-apoptotic effect.
Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy
Authors: Zhang Lilong , Chen Chen , Chai Dongqi , Li Chunlei , Kuang Tianrui , Liu Li , Dong Keshuai , Deng Wenhong , Wang Weixing 
Published: September 2022

Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy.Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327–1.711, p &lt; 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367–1.842, p &lt; 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360–0.703, p &lt; 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable.Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.
Metal-organic frameworks for hepatocellular carcinoma therapy and mechanism
Authors: Feng Yingqi , Wu Wei , Li Muzi 
Published: September 2022

In recent years, metal organic frameworks (MOFs) have attracted increasing attention in cancer therapy, because they can enhance the anticancer efficacy of photodynamic therapy (PDT), photothermal therapy (PTT), photoacoustic imaging, and drug delivery. Owing to stable chemical adjustability, MOFs can be used as carriers to provide excellent loading sites and protection for small-molecule drugs. In addition, MOFs can be used to combine with a variety of therapeutic drugs, including chemotherapeutics drugs, photosensitizers, and radiosensitizers, to efficiently deliver drugs to tumor tissue and achieve desired treatment. There is hardly any review regarding the application of MOFs in hepatocellular carcinoma. In this review, the design, structure, and potential applications of MOFs as nanoparticulate systems in the treatment of hepatocellular carcinoma are presented.Systematic Review Registration: website, identifier registration number
Warfarin anticoagulation management during the COVID-19 pandemic: The role of internet clinic and machine learning
Authors: Dai Meng-Fei , Li Shu-Yue , Zhang Ji-Fan , Wang Bao-Yan , Zhou Lin , Yu Feng , Xu Hang , Ge Wei-Hong 
Published: September 2022

Background: Patients who received warfarin require constant monitoring by hospital staff. However, social distancing and stay-at-home orders, which were universally adopted strategies to avoid the spread of COVID-19, led to unprecedented challenges. This study aimed to optimize warfarin treatment during the COVID-19 pandemic by determining the role of the Internet clinic and developing a machine learning (ML) model to predict anticoagulation quality.Methods: This retrospective study enrolled patients who received warfarin treatment in the hospital anticoagulation clinic (HAC) and “Internet + Anticoagulation clinic” (IAC) of the Nanjing Drum Tower Hospital between January 2020 and September 2021. The primary outcome was the anticoagulation quality of patients, which was evaluated by both the time in therapeutic range (TTR) and international normalized ratio (INR) variability. Anticoagulation quality and incidence of adverse events were compared between HAC and IAC. Furthermore, five ML algorithms were used to develop the anticoagulation quality prediction model, and the SHAP method was introduced to rank the feature importance.Results: Totally, 241 patients were included, comprising 145 patients in the HAC group and 96 patients in the IAC group. In the HAC group and IAC group, 73.1 and 69.8% (p = 0.576) of patients achieved good anticoagulation quality, with the average TTR being 79.9 ± 20.0% and 80.6 ± 21.1%, respectively. There was no significant difference in the incidence of adverse events between the two groups. Evaluating the five ML models using the test set, the accuracy of the XGBoost model was 0.767, and the area under the receiver operating characteristic curve was 0.808, which showed the best performance. The results of the SHAP method revealed that age, education, hypertension, aspirin, and amiodarone were the top five important features associated with poor anticoagulation quality.Conclusion: The IAC contributed to a novel management method for patients who received warfarin during the COVID-19 pandemic, as effective as HAC and with a low risk of virus transmission. The XGBoost model could accurately select patients at a high risk of poor anticoagulation quality, who could benefit from active intervention.
Apolipoprotein-A-I for severe COVID-19-induced hyperinflammatory states: A prospective case study
Authors: Faguer Stanislas , Del Bello Arnaud , Danet Chloé , Renaudineau Yves , Izopet Jacques , Kamar Nassim 
Published: September 2022

Viral infections can promote cytokine storm and multiorgan failure in individuals with an underlying immunosuppression or specific genetic background. Hyperinflammatory states, including critical forms of COVID-19, are characterized by a remodeling of the lipid profile including a dramatic decrease of the serum levels of apolipoprotein-A-I (ApoA-I), a protein known for its capacity to reduce systemic and lung inflammation, modulate innate and adaptive immunity, and prevent endothelial dysfunction and blood coagulation. In this study, four immunocompromised patients with severe COVID-19 cytokine storm that progressed despite standard-of-care therapy [Omicron (n = 3) and Delta (n = 1) variants] received 2– 4 infusions (10 mg/kg) of CER-001, an ApoA-I-containing HDL mimetic. Injections were well-tolerated with no serious adverse events. Three patients treated while not on mechanical ventilation had early clinical and biological improvement (oxygen withdrawal and correction of hematological and inflammatory parameters, including serum levels of interleukin-8) and were discharged from the hospital 3–4 days after CER-001 infusions. In the fourth patient who received CER-001 after orotracheal intubation for acute respiratory distress syndrome, infusions were followed by transient respiratory improvement before secondary worsening related to ventilation-associated pneumonia. This pilot uncontrolled exploratory compassionate study provides initial safety and proof-of-concept data from patients with a COVID-19 cytokine storm receiving ApoA-I. Further randomized controlled trial evaluation is now required to ascertain whether ApoA-I has any beneficial effects on patients with a COVID-19 cytokine storm.
Circular RNA hsa_circ_0003574 as a biomarker for prediction and diagnosis of ischemic stroke caused by intracranial atherosclerotic stenosis
Authors: Li Lingfei , Si Xiaoli , Ruan Jie , Ni Zhumei , Li Xiaoqin , Sang Hongfei , Xia Wenqing , Huang Jinyu , Liu Keqin , Lu Shan , Jiang Lin , Shao Anwen , Yin Congguo 
Published: September 2022

Background: Intracranial atherosclerotic stenosis (ICAS) is a common cause of first and recurrent ischemic stroke worldwide. Circular RNAs (circRNA)s have been recently suggested as candidate biomarkers in diagnosing and prognosis of ischemic stroke. A few circRNAs even serve as therapeutic targets that improves neurological function after ischemic stroke. However, the roles of circRNAs in ICAS caused ischemic stroke (ICAS-stroke) have not been fully understood. Therefore, in this study, we attempted to find some clues by investigating the different expression profiles of circRNAs between patients diagnosed with ICAS-stroke and normal control (NC)s.Methods: The OE Biotech Human ceRNA Microarray 4 × 180 K (47, 899 probes) screened circRNAs differentially expressed in peripheral blood in a discovery cohort (5 NCs versus five patients with ICAS-stroke). Afterwards, a validation cohort (31 NCs versus 48 patients with ICAS-stroke) was performed by quantitative polymerase chain reaction (qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and CircRNA–microRNA-mRNA interaction network was performed to identify potential interactions with microRNAs and pathway-deregulated circRNAs.Results: There were 244 circRNAs differentially expressed in patients diagnosed with ICAS-stroke compared with NCs [fold change (FC) ≥ 2.0 and p-value&lt;0.05]. Among the 244 circRNAs, 5 circRNAs (hsa_circ_0003574, hsa_circ_0010509, hsa_circ_0026628, hsa_circ_0074057, hsa_circ_0016993) were selected for following verification by qPCR. Only hsa_circRNA_0003574 was significantly upregulated in patients than in NCs. GO analysis indicated that predicted target genes involved various biological processes, cellular components, and molecular functions. KEGG analysis showed that many genes were enriched within the arginine and proline metabolism, pyrimidine metabolism, arginine and proline metabolism, lysosome, cytokine-cytokine receptor interaction, and RNA transport. The circRNA-miRNA-mRNA network analysis show the miRNAs that has_circ_0003574 likely interacts with.Conclusion: We observed that hsa_circRNA_0003574 is upregulated in patients with ICAS-stroke compared with NCs, indicating it may be a potential novel biomarker and therapeutic target for ICAS-stroke. In addition, we analyzed the laboratory results and found that homocysteine and glycosylated hemoglobin were elevated among ICAS-stroke patients. The relationship between hsa_circRNA_0003574 and these parameters requires further investigation.
Methotrexate showed efficacy both in Crohn’s disease and ulcerative colitis, predictors of surgery were identified in patients initially treated with methotrexate monotherapy
Authors: Wang Mengyao , Zhao Jingwen , Wang Heran , Zheng Changqing , Chang Bing , Sang Lixuan 
Published: September 2022

Objective: This study aimed to evaluate methotrexate efficacy in patients with Crohn’s disease (CD) and ulcerative colitis (UC), and identify predictors of surgery for patients who were initially treated with methotrexate monotherapy.Design: We performed a retrospective analysis of 34,860 patients with inflammatory bowel disease (IBD) in the IBD Bioresource (United Kingdom) prior to 9 November 2021. Logistic regression was used to identify factors associated with methotrexate efficacy. The data were randomly stratified into training and testing sets (7:3). Nomograms were developed based on Cox regression analysis outcomes. The predictive accuracy and discriminative ability were determined using the concordance index (C-index) and calibration curves.Results: Overall, 1,042 patients (CD: 791, UC: 251) were included. Independent factors associated with effective methotrexate monotherapy were younger age at diagnosis, latest therapy period, exclusive upper gastrointestinal tract disease (for CD), and longer duration between diagnosis and methotrexate initiation (for UC). For CD, predictors in the nomogram were gender, treatment era, tolerance, lesion site, perianal involvement, disease behaviour, and biologics requirements (C-index: 0.711 and 0.732 for training and validation cohorts, respectively). For UC, the factors were age at diagnosis and sex (C-index: 0.784 and 0.690 for training and validation cohorts, respectively). Calibration curves demonstrated good agreement between predictions and actual observations.
Machine-learning-derived radiomics signature of pericoronary tissue in coronary CT angiography associates with functional ischemia
Authors: Feng Yan , Xu Zhihan , Zhang Lin , Zhang Yaping , Xu Hao , Zhuang Xiaozhong , Zhang Hao , Xie Xueqian 
Published: September 2022

Objectives: To determine the association between radiomics signature (Rad-signature) of pericoronary tissue (PCT) in coronary computed tomography angiography (CCTA) and CT-derived fractional flow reserve (CT-FFR), and explore the influential factors of functional ischemia.Methods: We retrospectively included 350 patients who underwent CCTA from 2 centers, consisting of the training (n = 134), validation (n = 66), and testing (with CCTA and invasive coronary angiography, n = 150) groups. After evaluating coronary stenosis level in CCTA (anatomical CT), pericoronary fat attenuation index (FAI), and CT-FFR, we extracted 1,691 radiomic features from PCT. By accumulating and weighting the most contributive features to functional ischemia (CT-FFR ≤ 0.8) the Rad-signature was established using Boruta integrating with a random forest algorithm. Another 45 patients who underwent CCTA and invasive FFR were included to assure the performance of Rad-signature.Results: A total of 1046 vessels in 350 patients were analyzed, and functional ischemia was identified in 241/1046 (23.0%) vessels and 179/350 (51.1%) patients. From the 47 features highly relevant to functional ischemia, the top-8 contributive features were selected to establish Rad-signature. At the vessel level, the area under the curve (AUC) of Rad-signature to discriminate functional ischemia was 0.83, 0.82, and 0.82 in the training, validation, and testing groups, higher than 0.55, 0.55, and 0.52 of FAI (p &lt; 0.001), respectively, and was higher than 0.72 of anatomical CT in the testing group (p = 0.017). The AUC of the combined model (Rad-signature + anatomical CT) was 0.86, 0.85, and 0.83, respectively, significantly higher than that of anatomical CT and FAI (p &lt; 0.05). In the CCTA-invasive FFR group, using invasive FFR as the standard, the mean AUC of Rad-signature was 0.83 ± 0.02. At the patient level, multivariate logistic regression analysis showed that Rad-signature of left anterior descending (LAD) [odds ratio (OR) = 1.72; p = 0.012] and anatomical CT (OR = 3.53; p &lt; 0.001) were independent influential factors of functional ischemia (p &lt; 0.05). In the subgroup of nonobstructive (stenosis &lt;50% in invasive coronary angiography) and obstructive (≥50%) cases of the testing group, the independent factor of functional ischemia was FAI of LAD (OR = 1.10; p = 0.041) and Rad-signature of LAD (OR = 2.45; p = 0.042), respectively.Conclusion: The machine-learning-derived Rad-signature of PCT in CCTA demonstrates significant association with functional ischemia.
Transcription dynamics of heat shock proteins in response to thermal acclimation in Ostrinia furnacalis
Authors: Quan Yudong , Wang Zhenying , Wei Hongyi , He Kanglai 
Published: September 2022

Acclimation to abiotic stress plays a critical role in insect adaption and evolution, particularly during extreme climate events. Heat shock proteins (HSPs) are evolutionarily conserved molecular chaperones caused by abiotic and biotic stressors. Understanding the relationship between thermal acclimation and the expression of specific HSPs is essential for addressing the functions of HSP families. This study investigated this issue using the Asian corn borer Ostrinia furnacalis, one of the most important corn pests in China. The transcription of HSP genes was induced in larvae exposed to 33°C. Thereafter, the larvae were exposed to 43°C, for 2 h, and then allowed to recover at 27 C for 0, 0.5, 1, 2, 4, 6, and 8 h. At the recovery times 0.5–4 h, most population tolerates less around 1–3 h than without recovery (at 0 h) suffering continuous heat stress (43 C). There is no difference in the heat tolerance at 6 h recovery, with similar transcriptional levels of HSPs as the control. However, a significant thermal tolerance was observed after 8 h of the recovery time, with a higher level of HSP70. In addition, the transcription of HSP60 and HSC70 (heat shock cognate protein 70) genes did not show a significant effect. HSP70 or HSP90 significantly upregulated within 1–2 h sustained heat stress (43 C) but declined at 6 h. Our findings revealed extreme thermal stress induced quick onset of HSP70 or HSP90 transcription. It could be interpreted as an adaptation to the drastic and rapid temperature variation. The thermal tolerance of larvae is significantly enhanced after 6 h of recovery and possibly regulated by HSP70.