bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying liver metastasis-related hub genes in breast cancer and characterizing SPARCL1 as a potential prognostic biomarker
Authors: Chen Mingkuan , Zheng Wenfang , Fang Lin 
Published: May 2023

Background
The liver is the third most common metastatic site for advanced breast cancer (BC), and liver metastases predict poor prognoses. However, the characteristic biomarkers of BC liver metastases and the biological role of secreted protein acidic and rich in cysteine-like 1 (SPARCL1) in BC remain unclear. The present study aimed to identify potential biomarkers for liver metastasis of BC and to investigate the effect of SPARCL1 on BC.

Methods
The publicly available GSE124648 dataset was used to identify differentially expressed genes (DEGs) between BC and liver metastases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to annotate these DEGs and understand the biological functions in which they are involved. A protein–protein interaction (PPI) network was constructed to identify metastasis-related hub genes and further validated in a second independent dataset (GSE58708). Clinicopathological correlation of hub gene expression in patients with BC was determined. Gene set enrichment analysis (GSEA) was performed to explore DEG-related signaling pathways. SPARCL1 expression in BC tissues and cell lines was verified by RT-qPCR. Further in vitro experiments were performed to investigate the biological functions of SPARCL1 in BC cells.

Results
We identified 332 liver metastasis-related DEGs from GSE124648 and 30 hub genes, including SPARCL1, from the PPI network. GO and KEGG enrichment analyses of liver-metastasis-related DEGs revealed several enriched terms associated with the extracellular matrix and pathways in cancer. Clinicopathological correlation analysis of SPARCL1 revealed that its expression in BC was associated with age, TNM stage, estrogen receptor status, progesterone receptor status, histological type, molecular type, and living status of patients. GSEA results suggested that low SPARCL1 expression in BC was related to the cell cycle, DNA replication, oxidative phosphorylation, and homologous recombination. Lower expression levels of SPARCL1 were detected in BC tissues compared to adjacent tissues. The in vitro experiments showed that SPARCL1 knockdown significantly increased the proliferation and migration of BC cells, whereas the proliferation and migration were suppressed after elevating the expression of SPARCL1.

Conclusion
We identified SPARCL1 as a tumor suppressor in BC, which shows potential as a target for BC and liver metastasis therapy and diagnosis.
Effects of bamlanivimab alone or in combination with etesevimab on subsequent hospitalization and mortality in outpatients with COVID-19: a systematic review and meta-analysis
Authors: Tai Yu-Lin , Lee Ming-Dar , Chi Hsin , Chiu Nan-Chang , Lei Wei-Te , Weng Shun-Long , Liu Lawrence Yu-Min , Chen Chung-Chu , Huang Shih-Yu , Huang Ya-Ning , Lin Chien-Yu 
Published: May 2023

Background
Coronavirus disease 2019 (COVID-19) has caused an enormous loss of life worldwide. The spike protein of the severe acute respiratory syndrome coronavirus 2 is the cause of its virulence. Bamlanivimab, a recombinant monoclonal antibody, has been used alone or in combination with etesevimab to provide passive immunity and improve clinical outcomes. A systematic review and meta-analysis was conducted to investigate the therapeutic effects of bamlanivimab with or without etesevimab (BAM/ETE) treatment.

Methods
Our study was registered in PROSPERO (registry number CRD42021270206). We searched the following electronic databases, without language restrictions, until January 2023: PubMed, Embase, medRxiv, and the Cochrane database. A systematic review and meta-analysis was conducted based on the search results.

Results
Eighteen publications with a total of 28,577 patients were identified. Non-hospitalized patients given bamlanivimab with or without etesevimab had a significantly lower risk of subsequent hospitalization (18 trials, odds ratio (OR): 0.37, 95% confidence interval (CI): [0.29–0.49], I2: 69%; p < 0.01) and mortality (15 trials, OR: 0.27, 95% CI [0.17–0.43], I2: 0%; p = 0.85). Bamlanivimab monotherapy also reduced the subsequent risk of hospitalization (16 trials, OR: 0.43, 95% CI [0.34–0.54], I2: 57%; p = 0.01) and mortality (14 trials, OR: 0.28, 95% CI [0.17–0.46], I2: 0%; p = 0.9). Adverse events from these medications were uncommon and tolerable.

Conclusions
In this meta-analysis, we found the use of bamlanivimab with or without etesevimab contributed to a significantly-reduced risk of subsequent hospitalization and mortality in non-hospitalized COVID-19 patients. However, resistance to monoclonal antibodies was observed in COVID-19 variants, resulting in the halting of the clinical use of BAM/ETE. Clinicians’ experiences with BAM/ETE indicate the importance of genomic surveillance. BAM/ETE may be repurposed as a potential component of a cocktail regimen in treating future COVID variants.
Comprehensive identification and expression analysis of CAMTA gene family in Phyllostachys edulis under abiotic stress
Authors: Liu Ce , Tang Dingqin 
Published: May 2023

Background
Calmodulin-binding transcription factor (CAMTA) is a major transcription factor regulated by calmodulin (CaM) that plays an essential role in plant growth, development and response to biotic and abiotic stresses. The CAMTA gene family has been identified in Arabidopsis thaliana, rice (Oryza sativa) and other model plants, and its gene function in moso bamboo (Phyllostachys edulis) has not been identified.

Results
In this study, a total of 11 CAMTA genes were identified in P. edulis genome. Conserved domain and multiplex sequence alignment analysis showed that the structure between these genes was highly similar, with all members having CG-1 domains and some members having TIG and IQ domains. Phylogenetic relationship analysis showed that the CAMTA genes were divided into five subfamilies, and gene fragment replication promoted the evolution of this gene family. Promoter analysis revealed a large number of drought stress-related cis-acting elements in PeCAMTAs, and similarly high expression of the CAMTA gene family was found in drought stress response experiments, indicating the involvement of this gene family in drought stress. Gene expression pattern according to transcriptome data revealed participation of the PeCAMTA genes in tissue development.

Conclusions
Our results present new findings for the P. edulis CAMTA gene family and provide partial experimental evidence for further validation of the function of PeCAMTAs.
Hepatic nuclear factor 4 alpha promotes the ferroptosis of lung adenocarcinoma via transcriptional activation of cytochrome P450 oxidoreductase
Authors: Besskaya Valeria , Zhang Huan , Bian Yunyi , Liang Jiaqi , Bi Guoshu , Shan Guangyao , Zhan Cheng , Lin Zongwu 
Published: May 2023

Background
Lung adenocarcinoma is one of the most prevalent cancers while ferroptosis is crucial for cancer therapies. This study aims to investigate the function and mechanism of hepatic nuclear factor 4 alpha (HNF4A) in lung adenocarcinomas’ ferroptosis.

Materials and Methods
HNF4A expression in ferroptotic A549 cells was detected. Then HNF4A was knocked down in A549 cells while overexpressed in H23 cells. Cells with changed HNF4A expression were tested for cytotoxicity and the level of cellular lipid peroxidation. The expression of cytochrome P450 oxidoreductase (POR) expression was examined after HNF4A was knocked down or overexpressed. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) and dual-luciferase assays were performed to validate the regulation of HNF4A on POR. Finally, POR was restored in HNF4A-altered cells to check whether it restores the effect of HNF4A on ferroptosis.

Results
We found that HNF4A expression significantly decreased in the ferroptosis of A549 cells, and this change can be blocked by deferoxamine, an inhibitor of ferroptosis. Knockdown of HNF4A inhibited ferroptosis in A549 cells while overexpression of HNF4A promoted ferroptosis in H23 cells. We identified a key ferroptosis-related gene, POR serves as a potential target gene of HNF4A, whose expression was significantly changed in lung adenocarcinoma cells knocking down or overexpressing HNF4A. We demonstrated that HNF4A was bound to the POR’s promoter to enhance POR expression, and identified the binding sites via ChIP-qPCR and luciferase assays. Restoration of POR expression blocked the promoting effect of HNF4A on ferroptosis in lung adenocarcinoma.

Conclusion
HNF4A promotes POR expression through binding to the POR’s promoter, and subsequently promotes the ferroptosis of lung adenocarcinoma.
Preoperative Anxiety and Depression among Parents of Children undergoing Anesthesia and Surgical Operations in a Tertiary Hospital in Port Harcourt, Nigeria
Authors: Aggo A. T. , Okeafor C. U. 
Published: May 2023

Introduction: In spite of pediatric surgical interventions being potentially curative, and the advancement in pediatric anesthesiology, the fear of morbidity and mortality still abounds among parents. Anxiety and depressive symptoms among parents of children undergoing anesthesia and surgery could threaten postoperative recovery. This study therefore assessed the prevalence and factors of preoperative parental anxiety and depression.
Methodology: This was a cross-sectional study comprising of parents whose children were scheduled for surgery at the University of Port Harcourt Teaching Hospital, Rivers State, Nigeria. Preoperative anxiety and depression were the dependent variables, and were determined based on the Hamilton Anxiety Depression Scale (HADS), a validated and reliable tool. Socio-demographic and clinical-related variables comprised the independent variables. Bivariate and multivariate analyses were performed at 0.05 significant level.
Results: The study comprised a total of 100 parents whose children were undergoing surgical operations. The prevalence of preoperative parental anxiety and depression were 58.0% (95% CI: 48.3-67.7%) and 49.0% (95% CI:39.2-58.8%) respectively. Prevalence of preoperative parental anxiety was significantly higher among emergency surgeries (100.0%) in comparison to elective surgeries (56.5%) (p-value=0.034). The odds of preoperative parental anxiety was 50% lower with increasing existing number of children (AOR=0.505;95%CI:0.258-0.991). Parental depression had significantly lower odds with administration of general anesthesia (AOR= 0.022; 95%CI:0.001-0.701), and having higher existing number of children (AOR= 0.505; 95%CI:0.258-0.991).
Conclusion: The prevalence rates of preoperative anxiety and depression in the study setting are high. The findings highlight the need for evaluation of parental anxiety and depression pre-operatively especially those with single or lower number of children.
Significant Incidental Findings in the National Lung Screening Trial
Authors: Gareen Ilana F. , Gutman Roee , Sicks JoRean , Tailor Tina D. , Hoffman Richard M. , Trivedi Amal N. , Flores Efren , Underwood Ellen , Cochancela Jerson , Chiles Caroline 
Published: May 2023

ImportanceLow-dose computed tomography (LDCT) lung screening has been shown to reduce lung cancer mortality. Significant incidental findings (SIFs) have been widely reported in patients undergoing LDCT lung screening. However, the exact nature of these SIF findings has not been described.ObjectiveTo describe SIFs reported in the LDCT arm of the National Lung Screening Trial and classify SIFs as reportable or not reportable to the referring clinician (RC) using the American College of Radiology’s white papers on incidental findings.Design, Setting, and ParticipantsThis was a retrospective case series study of 26 455 participants in the National Lung Screening Trial who underwent at least 1 screening examination with LDCT. The trial was conducted from 2002 to 2009, and data were collected at 33 US academic medical centers.Main Outcomes and MeasuresSignificant incident findings were defined as a final diagnosis of a negative screen result with significant abnormalities that were not suspicious for lung cancer or a positive screen result with emphysema, significant cardiovascular abnormality, or significant abnormality above or below the diaphragm.ResultsOf 26 455 participants, 10 833 (41.0%) were women, the mean (SD) age was 61.4 (5.0) years, and there were 1179 (4.5%) Black, 470 (1.8%) Hispanic/Latino, and 24 123 (91.2%) White individuals. Participants were scheduled to undergo 3 screenings during the course of the trial; the present study included 75 126 LDCT screening examinations performed for 26 455 participants. A SIF was reported for 8954 (33.8%) of 26 455 participants who were screened with LDCT. Of screening tests with a SIF detected, 12 228 (89.1%) had a SIF considered reportable to the RC, with a higher proportion of reportable SIFs among those with a positive screen result for lung cancer (7632 [94.1%]) compared with those with a negative screen result (4596 [81.8%]). The most common SIFs reported included emphysema (8677 [43.0%] of 20 156 SIFs reported), coronary artery calcium (2432 [12.1%]), and masses or suspicious lesions (1493 [7.4%]). Masses included kidney (647 [3.2%]), liver (420 [2.1%]), adrenal (265 [1.3%]), and breast (161 [0.8%]) abnormalities. Classification was based on free-text comments; 2205 of 13 299 comments (16.6%) could not be classified. The hierarchical reporting of final diagnosis in NLST may have been associated with an overestimate of severe emphysema in participants with a positive screen result for lung cancer.Conclusions and RelevanceThis case series study found that SIFs were commonly reported in the LDCT arm of the National Lung Screening Trial, and most of these SIFs were considered reportable to the RC and likely to require follow-up. Future screening trials should standardize SIF reporting.
Perspectives of Rare Disease Experts on Newborn Genome Sequencing
Authors: Gold Nina B. , Adelson Sophia M. , Shah Nidhi , Williams Shardae , Bick Sarah L. , Zoltick Emilie S. , Gold Jessica I. , Strong Alanna , Ganetzky Rebecca , Roberts Amy E. , Walker Melissa , Holtz Alexander M. , Sankaran Vijay G. , Delmonte Ottavia , Tan Weizhen , Holm Ingrid A. , Thiagarajah Jay R. , Kamihara Junne , Comander Jason , Place Emily , Wiggs Janey , Green Robert C. 
Published: May 2023

ImportanceNewborn genome sequencing (NBSeq) can detect infants at risk for treatable disorders currently undetected by conventional newborn screening. Despite broad stakeholder support for NBSeq, the perspectives of rare disease experts regarding which diseases should be screened have not been ascertained.ObjectiveTo query rare disease experts about their perspectives on NBSeq and which gene-disease pairs they consider appropriate to evaluate in apparently healthy newborns.Design, Setting, and ParticipantsThis survey study, designed between November 2, 2021, and February 11, 2022, assessed experts’ perspectives on 6 statements related to NBSeq. Experts were also asked to indicate whether they would recommend including each of 649 gene-disease pairs associated with potentially treatable conditions in NBSeq. The survey was administered between February 11 and September 23, 2022, to 386 experts, including all 144 directors of accredited medical and laboratory genetics training programs in the US.ExposuresExpert perspectives on newborn screening using genome sequencing.Main Outcomes and MeasuresThe proportion of experts indicating agreement or disagreement with each survey statement and those who selected inclusion of each gene-disease pair were tabulated. Exploratory analyses of responses by gender and age were conducted using t and χ2 tests.ResultsOf 386 experts invited, 238 (61.7%) responded (mean [SD] age, 52.6 [12.8] years [range 27-93 years]; 126 [52.9%] women and 112 [47.1%] men). Among the experts who responded, 161 (87.9%) agreed that NBSeq for monogenic treatable disorders should be made available to all newborns; 107 (58.5%) agreed that NBSeq should include genes associated with treatable disorders, even if those conditions were low penetrance; 68 (37.2%) agreed that actionable adult-onset conditions should be sequenced in newborns to facilitate cascade testing in parents, and 51 (27.9%) agreed that NBSeq should include screening for conditions with no established therapies or management guidelines. The following 25 genes were recommended by 85% or more of the experts: OTC, G6PC, SLC37A4, CYP11B1, ARSB, F8, F9, SLC2A1, CYP17A1, RB1, IDS, GUSB, DMD, GLUD1, CYP11A1, GALNS, CPS1, PLPBP, ALDH7A1, SLC26A3, SLC25A15, SMPD1, GATM, SLC7A7, and NAGS. Including these, 42 gene-disease pairs were endorsed by at least 80% of experts, and 432 genes were endorsed by at least 50% of experts.Conclusions and RelevanceIn this survey study, rare disease experts broadly supported NBSeq for treatable conditions and demonstrated substantial concordance regarding the inclusion of a specific subset of genes in NBSeq.
In Situ Growth of Imine‐Bridged Anion‐Selective COF/AAO Membrane for Ion Current Rectification and Nanofluidic Osmotic Energy Conversion
Authors: Chen Mengyuan , Yang Kun , Wang Jin , Sun Hanjun , Xia Xing‐Hua , Wang Chen 
Published: May 2023

AbstractFacing the energy crisis, using the salinity gradient between seawater and freshwater for osmotic energy conversion is a direct way to obtain energy. So far, most nanofluidic membranes utilized for osmotic energy generation are cation‐selective. Given that both anion‐ and cation‐selective membranes have the identical importance for energy conversion devices, it is of great significance to develop anion‐selective membranes. Herein, an anion‐selective membrane is synthesized by in situ growth of imine‐bridged covalent organic framework (COF) on ordered anodic aluminum oxide (AAO) at room temperature. The imine groups and residual amino groups of COF can combine with protons in neutral solution, enabling the COF positively charged and efficiently transport of anions. Particularly, due to the asymmetry in the charge and structure of COF/AAO, the as‐prepared membrane exhibits excellent ionic current rectification property, which can inhibit ion concentration polarization effectively and possess high ion selectivity and permeability. Using the present COF/AAO membrane, salinity gradient energy can be successfully harvested from solutions with high salt content, and the output power density reached 17.95W m−2 under a 500‐fold salinity gradient. The study provides a new avenue for construction and application of anion‐selective membranes in the smart ion transport and efficient energy conversion.
Biomimetic Antithrombotic Tissue‐Engineered Vascular Grafts for Converting Cholesterol and Free Radicals into Nitric Oxide
Authors: Yang Dongcheng , Li Yanzhao , Tan Ju , Li Wenya , Xu Zilu , Xu Jianhua , Xu Wenhui , Hou Chunli , Zhou Jingting , Li Gang , Yang Mingcan , Liu Yong , Tang Qiaorui , Zhang Xiaohan , Zeng Wen , Feng Xuli , Zhu Chuhong 
Published: May 2023

AbstractSmall‐diameter tissue‐engineered vascular grafts (sdTEVGs) are essential materials used in bypass or replacement surgery for cardiovascular diseases; however, their application efficacy is limited because of patency rates, especially under hyperlipidemia, which is also clinically observed in patients with cardiovascular diseases. In such cases, improving sdTEVG patency is challenging because cholesterol crystals easily cause thrombosis and impede endothelialization. Herein, the development of a biomimetic antithrombotic sdTEVG incorporating cholesterol oxidase and arginine into biomineralized collagen–gold hydrogels on a sdTEVG surface is described. Biomimetic antithrombotic sdTEVGs represent a multifunctional substrate for the green utilization of hazardous substances and can convert cholesterol into hydrogen peroxide, which can react with arginine to generate nitric oxide (NO). NO is a vasodilator that can simulate the antithrombotic action of endothelial cells under hyperlipidemic conditions. In vivo studies show that sdTEVGs can rapidly produce large amounts of NO via a cholesterol catalytic cascade to inhibit platelet aggregation, thereby improving the blood flow velocity and patency rates 60 days after sdTEVG transplantation. A practical and reliable strategy for transforming “harmful” substances into “beneficial” factors at early transplantation stages is presented, which can also promote vascular transplantation in patients with hyperlipidemia.
Multiscale Anisotropic Scaffold Integrating 3D Printing and Electrospinning Techniques as a Heart‐on‐a‐Chip Platform for Evaluating Drug‐Induced Cardiotoxicity
Authors: Liu Sitian , Wang Zihan , Chen Xinyi , Han Mingying , Xu Jie , Li Ting , Yu Liu , Qin Maoyu , Long Meng , Li Mingchuan , Zhang Hongwu , Li Yanbing , Wang Ling , Huang Wenhua , Wu Yaobin 
Published: May 2023

AbstractCardiac safety assessments are significant in drug discovery, as drug‐induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart‐on‐a‐chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D‐printed micrometer‐scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched‐aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three‐layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self‐designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.
Enhancing Prosthetic Control through High‐Fidelity Myoelectric Mapping with Molecular Anchoring Technology
Authors: Pan Liang , Wang Hui , Huang Pingao , Wu Xuwei , Tang Zihan , Jiang Ying , Ji Shaobo , Cao Jinwei , Ji Baohua , Li Guanglin , Li Dechang , Wang Zhiming , Chen Xiaodong 
Published: May 2023

AbstractMyoelectric control utilizes electrical signals generated from the voluntary contraction of remaining muscles in an amputee's stump to operate a prosthesis. Precise and agile control requires low‐level myoelectric signals (below 10% of maximum voluntary contraction, MVC) from weak muscle contractions such as phantom finger or wrist movements, but imbalanced calcium concentration in atrophic skin can distort the signals. This is due to poor ionic–electronic coupling between skin and electrode, which often causes excessive muscle contraction, fatigue, and discomfort during delicate tasks. To overcome this challenge, a new strategy called molecular anchoring is developed to drive hydrophobic molecular effectively interact with and embed into stratum corneum for high coupling regions between ionic fluxes and electronic currents. The use of hydrophobic poly(N‐vinyl caprolactam) gel has resulted in an interface impedance of 20 kΩ, which is 1/100 of a commercial acrylic‐based electrode, allowing the detection of ultralow myoelectric signals (≈1.5% MVC) that approach human limits. With this molecular anchoring technology, amputees operate a prosthesis with greater dexterity, as phantom finger and wrist movements are predicted with 97.6% accuracy. This strategy provides the potential for a comfortable human–machine interface when amputees accomplish day‐to‐day tasks through precise and dexterous myoelectric control.