bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma
Authors: Zhu Zhenpeng , Lei Zhenchuan , Qian Jinqin , Zhang Cuijian , Gong Yanqing , Yin Guicao , Li Yifan , Li Xuesong , Lin Jian , Zhou Liqun 
Published: June 2022

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database.Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses.Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system.Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.
Immune Checkpoint Inhibitors Plus an Anti-VEGF Antibody as the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis and Cost-Effectiveness Analysis
Authors: Li Lu , Yang Shilei , Chen Yanwei , Tian Li , He Ying , Wu Bin , Dong Deshi 
Published: June 2022

Background: Sintilimab + a bevacizumab biosimilar (IBI305) (SB) and atezolizumab + bevacizumab (AB) have been approved for the treatment of unresectable hepatocellular carcinoma (HCC). At present, oncologists and their patients remain indecisive on their preferred treatment regime. Therefore, assessing their efficacy via a network meta-analysis and determining their comparative cost-effectiveness is necessary.Objective: To evaluate the cost-effectiveness of SB and AB compared with sorafenib alone for the treatment of unresectable HCC.Materials and Methods: The data used in our analysis were obtained from patients in ORIENT-32 and IMbrave150 phase III randomized clinical trials. A Bayesian network meta-analysis and cost-effectiveness analysis that included 1,072 patients were performed in this study. A partitioned survival model was applied to the patients with unresectable HCC. The model was designed with a 15-year time horizon, 1-month cycle, and 5% discount rate for costs and outcomes. In China, an incremental cost-effectiveness ratio (ICER) value of less than $33,500 (three times the GDP per capita in 2020) per quality-adjusted life-year (QALY) is considered cost-effective. The influence of parameter uncertainty on the results was verified by one-way deterministic sensitivity analysis and probability sensitivity analysis. Furthermore, scenario analyses of the patient assistance program (PAP) were conducted to explore the cost-effectiveness of SB and AB.Results: For the model of 1,072 patients, treatment with SB produced an additional 0.617 QALYs compared with sorafenib, resulting in an ICER of $39,766.86/QALY. Similarly, treatment with AB produced an additional 0.596 QALYs compared with sorafenib, resulting in an ICER of $103,037.66/QALY. The probability sensitivity analysis showed that when the willingness-to-pay (WTP) threshold was $33,500/QALY, the cost-effectiveness of SB and AB was 15.4 and 0.4%, respectively. However, in the scenario analyses, the probability of SB and AB regimens being cost-effective was 65.4 and 15.8%, respectively, at a WTP of $33,500/QALY.Conclusion: The findings from our study showed that sintilimab + a bevacizumab biosimilar is a cost-effective regimen compared with sorafenib as the first-line therapy for unresectable HCC in China at a $33,500 WTP threshold if sintilimab PAP is considered. However, the atezolizumab + bevacizumab regimen is not cost-effective whether atezolizumab PAP is considered or not.
Lenvatinib Combined With a PD-1 Inhibitor as Effective Therapy for Advanced Intrahepatic Cholangiocarcinoma
Authors: Xie Lulu , Huang Jingzheng , Wang Linling , Ren Wenrui , Tian Hao , Hu Anhong , Liang Jun , Jiao Yuqing , Li Yali , Zhou Qunfang , Zhang Wenjing 
Published: June 2022

Background: Lenvatinib combined with a PD-1 inhibitor has obtained a satisfactory antitumor effect in several solid tumors. However, the efficacy and tumor response of lenvatinib with a PD-1 inhibitor in advanced intrahepatic cholangiocarcinoma still need further exploration.Methods: This is a single-arm study for the assessment of the efficacy and tolerability of lenvatinib with a PD-1 inhibitor in intrahepatic cholangiocarcinoma patients who had chemotherapy failure. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1).Results: A total of 40 patients with advanced intrahepatic cholangiocarcinoma were enrolled after the chemorefractory effect. The median progression-free survival was 5.83 ± 0.76 months. The 3-month and 6-month progression-free survival rates were 80.0% and 32.5%, respectively. The median overall survival was 14.30 ± 1.30 months. The 12-month and 18-month overall survival rates were 61.4% and 34.7%. The 3-month RECIST 1.1 evaluation was that seven patients (17.5%) showed partial response, 23 patients (57.5%) had stable disease, and 10 patients (25.0%) had progressive disease. The objective response rate was 17.5%, and the disease control rate was 75.0%. All the recorded any-grade adverse events inducing treatment termination were controllable, and there were no AE-related deaths.Conclusion: Our study showed that a combination of lenvatinib with the PD-1 inhibitor could be an effective treatment for advanced intrahepatic cholangiocarcinoma after the chemorefractory effect.
Effectiveness and Nephrotoxicity of Intravenous Polymyxin B in Carbapenem-Resistant Gram-Negative Bacterial Infections Among Chinese Children
Authors: Jia Xuedong , Yin Zhao , Zhang Wan , Guo Conghui , Du Shuzhang , Zhang Xiaojian 
Published: June 2022

Background: No clinical study on the use of polymyxin B in Chinese children has been reported, thus making it difficult for pediatric clinicians to rationally select these drugs.Methods: A retrospective analysis of children treated with polymyxin B during hospitalization in a hospital from June 2019 to June 2021 was conducted to analyze its effectiveness and the incidence of acute kidney injury (AKI) during treatment with polymyxin B.Results: A total of 55 children were included in this study, and the results showed that the intravenous polymyxin B-based regimen had an effective rate of 52.7% in the treatment of Carbapenem-resistant Gram-negative bacterial (CR-GNB) infection in children. The results of the subgroup analysis showed that the course of treatment was longer in the favorable clinical response group than in the unfavorable outcome group (p = 0.027) and that electrolyte disturbances in children during the course of treatment could lead to unfavorable clinical outcomes (p = 0.042). The risk of incidence of AKI during treatment was 27.3%, and the all-cause mortality rate in the children on their discharge from the hospital was 7.3%.Conclusion: Polymyxin B can be used as a salvage therapy for CR-GNB infection in children when no other susceptible antibiotics are available, and the monitoring of kidney function should be strengthened.
Dissecting the Regulation of Arachidonic Acid Metabolites by Uncaria rhynchophylla (Miq). Miq. in Spontaneously Hypertensive Rats and the Predictive Target sEH in the Anti-Hypertensive Effect Based on Metabolomics and Molecular Docking
Authors: Gao Lei , Kong Xinqin , Wu Wenyong , Feng Zijin , Zhi Haijuan , Zhang Zijia , Long Huali , Lei Min , Hou Jinjun , Wu Wanying , Guo De-an 
Published: June 2022

Uncariarhynchophylla (Miq). Miq. (UR), as a traditional Chinese medicine, was employed in treating hypertension as a safe and effective therapy. The pharmacological properties of UR have characteristics of multiple biological targets and multiple functional pathways. Hypertension is related to impaired metabolic homeostasis and is especially associated with the abnormal regulation of arachidonic acid metabolites, the classical cardiovascular active compounds. This study aimed to examine the anti-hypertensive effect of UR extract (URE) and its regulating role in differential metabolic pathways. The results showed that daily administration of URE at a dose of 4 g crude drug/kg orally could exert hypotensive effects on spontaneously hypertensive rats (SHRs) for 8 weeks. Non-targeted metabolomics analysis of the plasma samples suggested that the anti-hypertension effect of URE in SHRs was associated with the reorganization of the perturbed metabolic network, such as the pathways of glycerophospholipid metabolism, linoleic acid metabolism, and arachidonic acid metabolism. For the targeted metabolomics, twenty-eight arachidonic acid metabolites in SHRs were quantitatively analyzed for the first time based on ultra-high performance liquid chromatography-tandem mass spectrometry method after URE administration. URE restored the functions of these cardiovascular active compounds and rebalanced the dynamics of arachidonic acid metabolic flux. Among them, the inhibition of soluble epoxide hydrolase (sEH) enzyme activity and up-regulation of vasodilators epoxyeicosatrienoic acids (EETs) were identified as contributors to the anti-hypertension effect of URE on SHRs, and sEH represented an attractive and promising drug-binding target of URE. With the molecular docking approach, 13 potential anti-hypertension ingredients as well as sEH inhibitors were discovered, which were worthy of further investigation and verification in future studies.
The Chemerin-CMKLR1 Axis is Functionally important for Central Regulation of Energy Homeostasis
Authors: Yun Haesung , Dumbell Rebecca , Hanna Katie , Bowen Junior , McLean Samantha L. , Kantamneni Sriharsha , Pors Klaus , Wu Qing-Feng , Helfer Gisela 
Published: June 2022

Chemerin is an adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism, and has been hypothesized as a link between obesity and type II diabetes. In humans affected by obesity, chemerin gene expression in peripheral tissues and circulating levels are elevated. In mice, plasma levels of chemerin are upregulated by high-fat feeding and gain and loss of function studies show an association of chemerin with body weight, food intake and glucose homeostasis. Therefore, chemerin is an important blood-borne mediator that, amongst its other functions, controls appetite and body weight. Almost all studies of chemerin to date have focused on its release from adipose tissue and its effects on peripheral tissues with the central effects largely overlooked. To demonstrate a central role of chemerin, we manipulated chemerin signaling in the hypothalamus, a brain region associated with appetite regulation, using pharmacological and genetic manipulation approaches. Firstly, the selective chemerin receptor CMKLR1 antagonist α-NETA was administered i.c.v. to rats to test for an acute physiological effect. Secondly, we designed a short-hairpin-RNA (shRNA) lentivirus construct targeting expression of CMKLR1. This shRNA construct, or a control construct was injected bilaterally into the arcuate nucleus of male Sprague Dawley rats on high-fat diet (45%). After surgery, rats were maintained on high-fat diet for 2 weeks and then switched to chow diet for a further 2 weeks. We found a significant weight loss acutely and inhibition of weight gain chronically. This difference became apparent after diet switch in arcuate nucleus-CMKLR1 knockdown rats. This was not accompanied by a difference in blood glucose levels. Interestingly, appetite-regulating neuropeptides remained unaltered, however, we found a significant reduction of the inflammatory marker TNF-α suggesting reduced expression of CMKLR1 protects from high-fat diet induced neuroinflammation. In white and brown adipose tissue, mRNA expression of chemerin, its receptors and markers of adipogenesis, lipogenesis and brown adipocyte activation remained unchanged confirming that the effects are driven by the brain. Our behavioral analyses suggest that knockdown of CMKLR1 had an impact on object recognition. Our data demonstrate that CMKLR1 is functionally important for the central effects of chemerin on body weight regulation and neuroinflammation.
Early and Late-Phase 24 h Responses of Stored Red Blood Cells to Recipient-Mimicking Conditions
Authors: Tzounakas Vassilis L. , Anastasiadi Alkmini T. , Karadimas Dimitrios G. , Velentzas Athanassios D. , Anastasopoulou Violetta I. , Papageorgiou Effie G. , Stamoulis Konstantinos , Papassideri Issidora S. , Kriebardis Anastasios G. , Antonelou Marianna H. 
Published: June 2022

The 24-hour (24 h) post-transfusion survival of donor red blood cells (RBCs) is an important marker of transfusion efficacy. Nonetheless, within that period, donated RBCs may encounter challenges able to evoke rapid stress-responses. The aim of the present study was to assess the effect of exposure to plasma and body temperature upon stored RBCs under recipient-mimicking conditions in vitro from the first hours “post-transfusion” up to 24 h. For this purpose, packed RBCs from seven leukoreduced CPD/SAGM units were reconstituted with plasma of twenty-seven healthy individuals and incubated for 24 h at 37oC. Three units were additionally used to examine stress-responses in 3-hour intervals post mixing with plasma (n = 5) until 24 h. All experiments were performed in shortly-, medium-, and long-stored RBCs. Hemolysis, redox, morphology, membrane protein binding and vesiculation parameters were assessed. Even though spontaneous hemolysis was minimal post-reconstitution, it presented a time-dependent increase. A similar time-course profile was evident for the concentration of procoagulant extracellular vesicles and the osmotic fragility (shortly-stored RBCs). On the contrary, mechanical fragility and reactive oxygen species accumulation were characterized by increases in medium-stored RBCs, evident even from the first hours in the recipient-mimicking environment. Finally, exposure to plasma resulted in rapid improvement of morphology, especially in medium-stored RBCs. Overall, some RBC properties vary significantly during the first 24 h post-mixing, at levels different from both the storage ones and the standard end-of-24 h. Such findings may be useful for understanding the performance of RBCs and their possible clinical effects −especially on susceptible recipients− during the first hours post-transfusion.
Effects of Acute Exposure to Polystyrene Nanoplastics on the Channel Catfish Larvae: Insights From Energy Metabolism and Transcriptomic Analysis
Authors: Jiang Qichen , Chen Xiaohui , Jiang Hucheng , Wang Minghua , Zhang Tongqing , Zhang Wenyi 
Published: June 2022

Microplastics (nanoplastics) pollution has been a major ecological issue threatening global aquatic ecosystems. However, knowledge of the adverse effects of nanoplastics and the effects on freshwater ecosystems is still limited. To understand the impacts of nanoplastics on freshwater ecosystems, it is essential to reveal the physiological changes caused by nanoplastics in freshwater organisms, especially at their early life-history stages. In the present study, the larval channel catfish Ietalurus punetaus were exposed to gradient concentrations (0, 5, 10, 25, and 50 mg/L) of 75-nm polystyrene nanoplastics (PS-NPs) for 24 h or 48 h, and changes in contents of energy metabolites, metabolic enzyme activities and transcriptome were assessed. The results showed that glucose and triglyceride contents increased after 24 h of exposure to 10 or 25 mg/L of PS-NPs but decreased with increased concentrations or prolonged exposure duration. Activities of most metabolic enzymes analyzed decreased in the larvae after 48 h of exposure, especially in 25 or 50 mg/L of PS-NPs. These suggested that PS-NPs caused huge energy consumption and disturbed the energy metabolism in larval fish. Transcriptomic analysis showed that 48 h of exposure to 50 mg/L PS-NPs affected the expression of genes involved in protein digestion and induced response of proteasomes or heat shock proteins in the larval I. punetaus. The genes involved in peroxisome proliferator-activated receptors (PPAR) pathway and biosynthesis of amino acids were activated after the exposure. PS-NPs also depressed the expression of the genes involved in gonad development or muscle contraction in the larval I. punetaus. Overall, acute exposure to 75-nm PS-NPs disrupted the energy metabolism by consuming the energy reserves, and affected a series of molecular pathways which may further affect the development and survival of fish. This study provided the information about adverse effects of nanoplastics on the fish larvae and revealed the molecular pathways for the potential adverse outcomes.
Evaluation of Psychometric Properties of Hardiness Scales: A Systematic Review
Authors: Sharif Nia Hamid , Froelicher Erika Sivarajan , Hosseini Lida , Ashghali Farahani Mansoureh 
Published: June 2022

BackgroundHardiness is one of the personality traits that can help individuals in stressful situations. Since human beings are constantly under stressful situations and the stresses inflicted on people in each situation are different, various scales have been developed for assessing this feature among different people in different situations. Hence, it becomes necessary for researchers and health workers to assess this concept with valid and reliable scales. This systematic review aims to rigorously assess the methodological quality and psychometric properties of hardiness scales.MethodIn the first step, the databases including Scopus, PubMed, Web of science, and Persian databases were searched using suitable keywords without limitation time. We select eligible suitable studies after screening titles and abstracts. The quality of studies was evaluated using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist and the Terwee quality criteria.ResultOf the 747 articles identified, 33 articles were entered in this study. Based on the COSMIN checklist, the most reported properties were as following structural validity (84%), hypothesis testing (56%), content validity (42%), and internal consistency (39%). Furthermore, 12 studies reported cross-cultural validity, three studies criterion validity, and one study reported measurement error.ConclusionThe “family caregivers’ hardiness scale,” “Japanese Athletic Hardiness Scale,” “Occupational Hardiness Questionnaire,” and “Children’s Hardiness Scale” are the best tools for assessing hardiness in family caregivers, athletes, employees, and children respectively. In addition, the “Dispositional Resilience Scale” (DRS-15) and The Personal Views Survey (PVS III-R) are the most frequently used scales with suitable features for measuring hardiness in the general population.
Strength-Cognitive Training: A Systemic Review in Adults and Older Adults, and Guidelines to Promote “Strength Exergaming” Innovations
Authors: Esmaeilzadeh Samad , Kumpulainen Susanne , Pesola Arto J. 
Published: June 2022

BackgroundDespite functional and cognitive benefits, few adults and older adults do strength training twice per week with sufficient intensity. Exercise-based active video games (exergaming) may amplify the cognitive benefits of exercise and increase adherence and motivation toward training. However, the benefits of a well-defined and monitored dose of strength training, executed simultaneously or sequentially with a cognitive element, has received little attention. In this study we have two aims: First, to systematically gather the available evidence; second, to suggest possible ways to promote strength exergaming innovations.MethodsWe systematically reviewed randomized controlled trials using simultaneous or sequent combined strength and cognitive training or strength exergaming to improve cognitive or functional outcomes in adults and older adults.ResultsAfter screening 1,785 studies (Google Scholar, ACM Digital Library, IEEE Xplore Library, PsycARTICLES, Scopus, Cochrane Library and PubMed) we found three eligible studies. Of the two studies using sequent strength and cognitive training, one showed improved functionality, but the other showed negative effects on cognition. The third study using simultaneous intervention, reported a positive influence on both cognition and function, when compared with either strength training alone or a control group. Moderate level of evidence was showed on GRADE analysis.ConclusionThe existing little evidence suggests that strength and cognitive training improves cognition and function in adults and older adults. The following suggestions may help to promote further innovation: (1) ensure minimal dosage of strength training (30–60 min, 2 × /week), (2) use machine-based strength training devices to control volume and intensity (to prevent cognitive components from interfering with strength training), (3) include power training by using cognitive tasks requiring rapid reactions, and (4) add cognitive memory tasks (to extend the cognitive benefits of strength training per se), and (5) include motivational exergame elements to increase adherence.