bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of a novel cuproptosis-related lncRNA signature associated with prognosis and tumor matrix features to predict immunotherapy in soft tissue carcinoma
Authors: Liu Binfeng , Pang Ke , Feng Chengyao , Liu Zhongyue , Li Chenbei , Zhang Haixia , Liu Ping , Li Zhihong , He Shasha , Tu Chao 
Published: December 2022

Background: A crucial part of the malignant processes of soft tissue sarcoma (STS) is played by cuproptosis and lncRNAs. However, the connection between cuproptosis-related lncRNAs (CRLs) and STS is nevertheless unclear. As a result, our objective was to look into the immunological activity, clinical significance, and predictive accuracy of CRLs in STS.Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, respectively, provided information on the expression patterns of STS patients and the general population. Cuproptosis-related lncRNA signature (CRLncSig) construction involved the univariate, multivariate, and least absolute shrinkage and selection operator Cox regression analysis. The predictive performance of the CRLncSig was evaluated using a serial analysis. Further research was done on the connections between the CRLncSig and the tumor immune milieu, somatic mutation, immunotherapy response, and chemotherapeutic drug susceptibility. Notably, an in vitro investigation served to finally validate the expression of the hallmark CRLs.Results: A novel efficient CRLncSig composed of seven CRLs was successfully constructed. Additionally, the low-CRLncSig group’s prognosis was better than that of the high-CRLncSig group’s based on the new CRLncSig. The innovative CRLncSig then demonstrated outstanding, consistent, and independent prognostic and predictive usefulness for patients with STS, according to the evaluation and validation data. The low-CRLncSig group’s patients also displayed improved immunoreactivity phenotype, increased immune infiltration abundance and checkpoint expression, and superior immunotherapy response, whereas those in the high-CRLncSig group with worse immune status, increased tumor stemness, and higher collagen levels in the extracellular matrix. Additionally, there is a noticeable disparity in the sensitivity of widely used anti-cancer drugs amongst various populations. What’s more, the nomogram constructed based on CRLncSig and clinical characteristics of patients also showed good predictive ability. Importantly, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) demonstrated that the signature CRLs exhibited a significantly differential expression level in STS cell lines.Conclusion: In summary, this study revealed the novel CRLncSig could be used as a promising predictor for prognosis prediction, immune activity, tumor immune microenvironment, immune response, and chemotherapeutic drug susceptibility in patients with STS. This may provide an important direction for the clinical decision-making and personalized therapy of STS.
Upregulation of leucine-rich alpha-2 glycoprotein: A key regulator of inflammation and joint fibrosis in patients with severe knee osteoarthritis
Authors: Sarkar Ashish , Chakraborty Debolina , Kumar Vijay , Malhotra Rajesh , Biswas Sagarika 
Published: December 2022

IntroductionOsteoarthritis (OA) is a degenerative disease of the joints mainly affecting older individuals. Since the etiology behind the progression of OA is not well understood, several associated consequences, such as synovial joint stiffness and its progression due to joint fibrosis, are still poorly understood. Although a lot of developments have been achieved in the diagnosis and management of OA, synovial fibrosis remains one of the major challenging consequences. The present study was therefore focused on understanding the mechanism of synovial fibrosis, which may further contribute to improving symptomatic treatments, leading to overall improvements in the treatment outcomes of patients with OA.MethodsWe used advanced proteomic techniques including isobaric tag for relative and absolute quantitation and sequential window acquisition of all theoretical mass spectra for the identification of differentially expressed proteins in the plasma samples of patients with OA. An in silico study was carried out to evaluate the association of the identified proteins with their biological processes related to fibrosis and remodeling of the extracellular matrix (ECM). The most significantly upregulated protein was then validated by Western blot and enzyme-linked immunosorbent assay. The target protein was then further investigated for its role in inflammation and joint fibrosis using an in vitro study model.ResultsLeucine-rich alpha-2 glycoprotein (LRG1) was found to be the most highly differentially expressed upregulated (9.4-fold) protein in the plasma samples of patients with OA compared to healthy controls. The knockdown of LRG1 followed by in vitro studies revealed that this protein promotes the secretion of the ECM in synovial cells and actively plays a role in wound healing and cell migration. The knockdown of LRG1 further confirmed the reduction of the inflammatory- and fibrosis-related markers in primary cells.ConclusionLRG1 was identified as a highly significant upregulated protein in the plasma samples of patients with OA. It was found to be associated with increased fibrosis and cell migration, leading to enhanced inflammation and joint stiffness in OA pathogenesis.
The CMV-encoded G protein-coupled receptors M33 and US28 play pleiotropic roles in immune evasion and alter host T cell responses
Authors: White Timothy M. , Bonavita Cassandra M. , Stanfield Brent A. , Farrell Helen E. , Davis-Poynter Nicholas J. , Cardin Rhonda D. 
Published: December 2022

IntroductionHuman cytomegalovirus (HCMV) is a global health threat due to its ubiquity and lifelong persistence in infected people. During latency, host CD8+ T cell responses to HCMV continue to increase in a phenomenon known as memory inflation. We used murine CMV (MCMV) as a model for HCMV to characterize the memory inflation response to wild-type MCMV (KP) and a latency-defective mutant (ΔM33stop), which lacks M33, an MCMV chemokine receptor homolog. M33 is essential for normal reactivation from latency and this was leveraged to determine whether reactivation in vivo contributes to T cell memory inflation.MethodsMice were infected with wild-type or mutant MCMV and T cell responses were analyzed by flow cytometry at acute and latent time points. Ex vivo reactivation and cytotoxicity assays were carried out to further investigate immunity and virus replication. Quantitative reverse-transcriptase polymerase chain reaction (q-RTPCR) was used to examine gene expression during reactivation. MHC expression on infected cells was analyzed by flow cytometry. Finally, T cells were depleted from latently-infected B cell-deficient mice to examine the in vivo difference in reactivation between wild-type and ΔM33stop.ResultsWe found that ΔM33stop triggers memory inflation specific for peptides derived from the immediate-early protein IE1 but not the early protein m164, in contrast to wild-type MCMV. During ex vivo reactivation, gene expression in DM33stop-infected lung tissues was delayed compared to wild-type virus. Normal gene expression was partially rescued by substitution of the HCMV US28 open reading frame in place of the M33 gene. In vivo depletion of T cells in immunoglobulin heavy chain-knockout mice resulted in reactivation of wild-type MCMV, but not ΔM33stop, confirming the role of M33 during reactivation from latency. Further, we found that M33 induces isotype-specific downregulation of MHC class I on the cell surface suggesting previously unappreciated roles in immune evasion.DiscussionOur results indicate that M33 is more polyfunctional than previously appreciated. In addition to its role in reactivation, which had been previously described, we found that M33 alters viral gene expression, host T cell memory inflation, and MHC class I expression. US28 was able to partially complement most functions of M33, suggesting that its role in HCMV infection may be similarly pleotropic.
PD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer: A real-world retrospective cohort study
Authors: Chen Shubin , Wei Haowen , Zhao Wenhua , Jiang Wei , Ning Ruiling , Zhou Shaozhang , Tan Liping , Wang Huilin , Su Cuiyun , He Jianbo , Zeng Aiping , Zhao Yun , Yu Qitao 
Published: December 2022

BackgroundThe aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer.MethodsIn this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents’ group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox’s proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis.ResultsThe average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group.ConclusionPD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.
A mucosal recovery software tool for endoscopic submucosal dissection in early gastric cancer
Authors: Zhao Yinuo , Wang Huogen , Fan Yanyan , Jin Chaohui , Xu Qinwei , Jing Jiyong , Zhang Tianqiao , Zhang Xuedong , Chen Wanyuan 
Published: December 2022

BackgroundDue to the limited diagnostic ability, the low detection rate of early gastric cancer (EGC) is a serious health threat. The establishment of the mapping between endoscopic images and pathological images can rapidly improve the diagnostic ability to detect EGC. To expedite the learning process of EGC diagnosis, a mucosal recovery map for the mapping between ESD mucosa specimen and pathological images should be performed in collaboration with endoscopists and pathologists, which is a time-consuming and laborious work.Methods20 patients at the Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College from March 2020 to July 2020 were enrolled in this study. We proposed the improved U-Net to obtain WSI-level segmentation results, and the WSI-level results can be mapped to the macroscopic image of the specimen. For the convenient use, a software pipeline named as “Pathology Helper” for integration the workflow of the construction of mucosal recovery maps was developed.ResultsThe MIoU and Dice of our model can achieve 0.955 ± 0.0936 and 0.961 ± 0.0874 for WSI-level segmentation, respectively. With the help of “Pathology Helper”, we can construct the high-quality mucosal recovery maps to reduce the workload of endoscopists and pathologists.Conclusion“Pathology Helper” will accelerate the learning of endoscopists and pathologists, and rapidly improve their abilities to detect EGC. Our work can also improve the detection rate of early gastric cancer, so that more patients with gastric cancer will be treated in a timely manner.
Development and validation of a new set of indicators to assess the quality of maternal and child nutritional care at the primary care
Authors: Ancira-Moreno Monica , Omaña-Guzmán Isabel , Bautista-Morales Arturo Cuauhtémoc , Acosta-Ruiz Omar , Hernández Cordero Sonia , Burrola-Méndez Soraya , Vilar-Compte Mireya , Monterrubio Flores Eric , Kaufer-Horwitz Martha , Pérez Navarro Cecilia , Muñoz-Manrique Cinthya , Mazariegos Mónica , Trejo-Domínguez Alejandra , Sánchez Muzquiz Belen , Cajero Ariana , Brero Mauro , Sachse Matthias , Cobo Armijo Fernanda 
Published: December 2022

IntroductionMaternal and child malnutrition is a worldwide public health problem with short, medium, and long-term adverse consequences for both mother and child. In Mexico, maternal and child malnutrition represents a serious public health problem that must be urgently addressed. In this context, Primary Health Care (PHC) plays an important role in the prevention, detection, monitoring, and treatment of the different forms of maternal and child malnutrition. Assessing the quality of nutritional care offered at this level of care is necessary in order to improve it; however, there are no indicators for the evaluation of this quality. Therefore, this study aimed at developing a set of indicators to assess the quality of maternal and child nutritional care at PHC.MethodsWe developed indicators for different stages of life: preconception, pregnancy, infancy, and preschool age. A systematic review of the literature on clinical guidelines for the prevention, diagnosis, and treatment of the different forms of malnutrition was carried out; the recommendations of the guidelines evaluated with good quality were extracted.ResultsBased on these recommendations, 22 indicators were constructed. A pilot study was carried out to validate the indicators and 16 indicators were selected to assess the maternal and child nutritional care at PHC.
A comparative study of gastric histopathology sub-size image classification: From linear regression to visual transformer
Authors: Hu Weiming , Chen Haoyuan , Liu Wanli , Li Xiaoyan , Sun Hongzan , Huang Xinyu , Grzegorzek Marcin , Li Chen 
Published: December 2022

IntroductionGastric cancer is the fifth most common cancer in the world. At the same time, it is also the fourth most deadly cancer. Early detection of cancer exists as a guide for the treatment of gastric cancer. Nowadays, computer technology has advanced rapidly to assist physicians in the diagnosis of pathological pictures of gastric cancer. Ensemble learning is a way to improve the accuracy of algorithms, and finding multiple learning models with complementarity types is the basis of ensemble learning. Therefore, this paper compares the performance of multiple algorithms in anticipation of applying ensemble learning to a practical gastric cancer classification problem.MethodsThe complementarity of sub-size pathology image classifiers when machine performance is insufficient is explored in this experimental platform. We choose seven classical machine learning classifiers and four deep learning classifiers for classification experiments on the GasHisSDB database. Among them, classical machine learning algorithms extract five different image virtual features to match multiple classifier algorithms. For deep learning, we choose three convolutional neural network classifiers. In addition, we also choose a novel Transformer-based classifier.ResultsThe experimental platform, in which a large number of classical machine learning and deep learning methods are performed, demonstrates that there are differences in the performance of different classifiers on GasHisSDB. Classical machine learning models exist for classifiers that classify Abnormal categories very well, while classifiers that excel in classifying Normal categories also exist. Deep learning models also exist with multiple models that can be complementarity.DiscussionSuitable classifiers are selected for ensemble learning, when machine performance is insufficient. This experimental platform demonstrates that multiple classifiers are indeed complementarity and can improve the efficiency of ensemble learning. This can better assist doctors in diagnosis, improve the detection of gastric cancer, and increase the cure rate.
Efficacy of positive airway pressure therapy and high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: A protocol for systematic review and network meta-analysis
Authors: Niu Jianyi , He Zhenfeng , Zha Shanshan , Huang Qiaoyun , Fu Wei , Feng Shengchuan , Guan Lili , Zhou Luqian , Chen Rongchang 
Published: December 2022

IntroductionPositive airway pressure (PAP) therapy is currently the first-line respiratory support technique for acute respiratory failure (ARF) due to acute cardiogenic pulmonary edema (ACPE), but the accompanied adverse events and patient's intolerance with treatment in some cases limited its use in clinical practice. Some recent trials indicated that high-flow nasal cannula oxygen (HFNO) is a promising alternative to PAP therapy. In order to choose the optimum treatment for patients with ACPE, this network meta-analysis will firstly compares the efficacy of HFNO, PAP, and conventional oxygen therapy (COT).Methods and analysisThe Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement and its extension for network meta-analysis will be followed in the conduct of this investigation. We will examine these databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. The ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform Search Portal will be used to search ongoing trials. Only randomized controlled trials meeting the eligibility criteria will be included. Through the Cochrane Collaboration's tool, the included studies' risk of bias will be assessed. The pairwise meta-analysis will be performed with RevMan 5.4.1 software. A Bayesian network meta-analysis will use random-effects models to derive odds ratios for the treatment effects of all interventions compared to each other using R software (version 3.6.1), and the rjags and gemtc packages. The Q statistic and I2 index will be used for investigating the heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence.
CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration
Authors: Mueller Franziska , Fabritius Matthias P. , Stueckelschweiger Lena , Kiesl Sophia , Moench Sebastian , Tiedt Steffen , Rémi Jan , Kellert Lars , Herzberg Moriz , Küpper Clemens , Dimitriadis Konstantinos , Ricke Jens , Puhr-Westerheide Daniel , Liebig Thomas , Kunz Wolfgang G. , Reidler Paul 
Published: December 2022

ObjectivesLarge vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients.ResultsWe included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p &lt; 0.001) and lower ASPECTS (median: 8 vs. 9, p &lt; 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (β = −0.25, p = 0.004) but not with TFSO (β = −0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (β = −0.39 vs. β = −0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p &lt; 0.001).ConclusionImaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.
Development and validation of a dynamic risk prediction system for constipation in patients with amyotrophic lateral sclerosis
Authors: Niu Tongyang , Zhou Xiaomeng , Li Xin , Liu Tingting , Liu Qi , Li Rui , Liu Yaling , Dong Hui 
Published: December 2022

IntroductionAlthough constipation is a common non-motor symptom in patients with amyotrophic lateral sclerosis (ALS), it is poorly valued. Moreover, there is a bidirectional effect between constipation and neuropsychiatric and sleep disturbances. Thus, these symptoms are better treated simultaneously. Therefore, this study aimed to develop and validate a model for predicting the risk of constipation in ALS patients, to help clinicians identify and treat constipation early.MethodsData of 118 ALS admissions from an observational prospective cohort, registered between March 2017 and December 2021, were analyzed. Demographic data were obtained. Constipation was assessed using the Knowles–Eccersley–Scott Symptom Questionnaire. The severity of ALS was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Anxiety and depressive symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). The Pittsburgh Sleep Quality Index (PSQI) was used to assess patients' sleep status. The least absolute shrinkage and selection operator (LASSO) regression model was used to select factors and construct a nomogram. Nomogram model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). The model was internally validated using bootstrap validation in the current cohort.ResultsAge, family history of constipation, total ALSFRS-R score, site of onset, total PSQI score, and depressed, were identified as significant predictors of the risk of constipation in ALS patients. The prediction model was validated to have good accuracy (Hosmer–Lemeshow test: χ2 = 11.11, P &gt; 0.05) and discrimination (AUC = 0.856, 95% confidence interval: 0.784–0.928). DCA and CIC showed that the nomogram model had excellent clinical performance.ConclusionsA web-based ALS constipation risk calculator with good predictive performance was constructed to identify patients at high risk of constipation and to allow early intervention in a clinical context.