bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving prenatal diagnosis with combined karyotyping, CNV-seq and QF-PCR: a comprehensive analysis of chromosomal abnormalities in high-risk pregnancies
Authors: Liu Jia-pei , Wang Shan-Bing , Luo Li , Guo Ya-mei 
Published: January 2025

ObjectiveThis study aims to assess the diagnostic efficacy of a combined approach integrating chromosomal karyotyping, copy number variation sequencing (CNV-seq), and quantitative fluorescence polymerase chain reaction (QF-PCR) in detecting chromosomal abnormalities in high-risk pregnancies.MethodsThis retrospective study analyzed 617 high-risk pregnancies undergoing prenatal diagnosis from February 2023 to August 2024, with amniotic fluid samples concurrently analyzed using karyotyping, CNV-seq, and QF-PCR. We evaluated clinical characteristics, diagnostic yields, and inter-method concordance rates. Longitudinal follow-up assessed pregnancy outcomes and neonatal phenotypes, with particular emphasis on cases demonstrating diagnostic discrepancies or variants of uncertain clinical significance.ResultsThe integrated approach detected chromosomal abnormalities in 12.5% (77/617) of cases, significantly higher than the rates achieved by karyotyping alone (9.7%) and CNV-seq/QF-PCR alone (8.3%) (p &lt; 0.05). Karyotyping showed full concordance with CNV-seq and QF-PCR in detecting major chromosomal aneuploidies, identifying 21 cases of trisomy 21 and 4 cases of trisomy 18. CNV-seq uniquely identified additional pathogenic copy number variations in 2.1% of cases and variants of uncertain significance (VUS) in 3.2% of cases, both undetectable by conventional karyotyping. Subjects with high-risk non-invasive prenatal testing (NIPT) results had the highest abnormality detection rate (57.6%, p &lt; 0.05). Follow-up data revealed pregnancy termination in 44 of 97 cases with chromosomal abnormalities. Notably, neonates carrying pathogenic CNVs inherited from asymptomatic parents demonstrated normal phenotypes.ConclusionThe integration of karyotyping, CNV-seq, and QF-PCR provides superior diagnostic yield compared to individual testing strategies in high-risk pregnancies. Although karyotyping remains the gold standard for detecting major chromosomal aberrations, CNV-seq and QF-PCR enhance diagnostic precision through detection of submicroscopic variations. Multi-center studies with larger cohorts are needed to confirm these findings and clarify the clinical significance of uncertain variants.
Exploring potential therapeutic targets for small cell lung cancer based on transcriptomics combined with Mendelian randomization analysis
Authors: Liao Zhicheng , Jia Pengcheng , Li Yifan , Zheng Zhihui , Zhang Jizhou 
Published: January 2025

ObjectiveThe main objective of this study was to explore and identify new genetic targets in small-cell lung cancer (SCLC) through transcriptomics analysis and Mendelian randomization (MR) analysis, which will help in the subsequent development of new therapeutic interventions.MethodsIn this study, we extracted the SCLC dataset from the Gene Expression Omnibus (GEO) database, processed the data, and screened out differentially expressed genes (DEGs) using R software. Based on expression quantitative trait loci data and the genome-wide association study data of SCLC, MR analysis was used to screen the genes closely related to SCLC disease, which intersect with DEGs to obtain co-expressed genes (CEGs), and the biological functions and pathways of CEGs were further explored by enrichment analysis. In addition, the CIBERSORT algorithm was applied to assess the level of immune cell infiltration in SCLC and to analyze the correlation between CEGs and immune cells. Meanwhile, we performed a survival analysis on these five CEGs using an independent cohort of SCLC patients. Finally, the results for the target genes were validated.ResultsIn this study, 857 DEGs were identified, including 443 up-regulated and 414 down-regulated genes, and 5 CEGs (PSAT1, PSRC1, COLEC12, PLLP, HP) that were significantly associated with SCLC were identified through further intersecting. The results of enrichment analyses indicated that CEGs play important roles in several key functions and pathways. Immune-cell-related analysis revealed the unique distribution of immune cell infiltration in SCLC and the mechanism of immune cell regulation by CEGs. Survival analysis results indicated that PSRC1 was significantly correlated with the overall survival of SCLC, and the survival rate of the high-expression group was markedly lower than that of the low-expression group. Finally, the consistency of the results between the validation group analyses and MR analysis confirmed that the results of this study is reliable.ConclusionThe CEGs and their associated functions and pathways screened in this study may be potential targets of therapeutic intervention in SCLC by targeting specific molecular pathways.
The bronchoalveolar lavage fluid CD44 as a marker for pulmonary fibrosis in diffuse parenchymal lung diseases
Authors: Suchankova Magda , Zsemlye Eszter , Urban Jan , Baráth Peter , Kohútová Lenka , Siváková Barbara , Ganovska Martina , Tibenska Elena , Szaboova Kinga , Tedlova Eva , Juskanic Dominik , Kluckova Kristina , Kardohelyova Michaela , Moskalets Tetiana , Ohradanova-Repic Anna , Babulic Patrik , Bucova Maria , Leksa Vladimir 
Published: January 2025

IntroductionDiffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition. The major hallmark of lung fibrosis is uncontrolled activation of lung fibroblasts to myofibroblasts associated with extracellular matrix deposition and the loss of both lung structure and function.MethodsHere, we used this peculiar feature in order to identify specific biomarkers of pulmonary fibrosis in bronchoalveolar lavage fluids (BALF). The primary MRC-5 human fibroblasts were activated with BALF collected from patients with clinically diagnosed lung fibrosis; the activated fibroblasts were then washed rigorously, and further incubated to allow secretion. Afterwards, the secretomes were analysed by mass spectrometry.ResultsIn this way, the CD44 protein was identified; consequently, BALF of all DPLD patients were positively tested for the presence of CD44 by ELISA. Finally, biochemical and biophysical characterizations revealed an exosomal origin of CD44. Receiver operating characteristics curve analysis confirmed CD44 in BALF as a specific and reliable biomarker of IPF and other types of DPLD accompanied with pulmonary fibrosis.
Case report: Efgartigimod is a novel therapeutic option for ocular myasthenia gravis: a report of 2 cases
Authors: Ma Tianying , Zhu Ying , Zhu Ruixia 
Published: January 2025

IntroductionEfgartigimod has been approved for the treatment of acetylcholine receptor antibodies-positive generalized myasthenia gravis (AChR-Ab+gMG), but its efficacy in patients with ocular myasthenia gravis (OMG) is not known.Case presentationWe describe 2 cases of patients with AChR-Ab+ OMG who showed unfavorable responses to corticosteroids and tacrolimus. Within 2 weeks of initiating efgartigimod, both patients showed rapid improvement and minimal symptom expression was achieved in weeks 3 to 4, which was maintained up to week 12.ConclusionThe 2 cases described herein provide preliminary evidence for the effectiveness of efgartigimod for the treatment of OMG for patients who do not respond or are intolerant to conventional medications. Large-scale studies are needed to confirm these findings.
Analysis of whole transcriptome reveals the immune response to porcine reproductive and respiratory syndrome virus infection and tylvalosin tartrate treatment in the porcine alveolar macrophages
Authors: Du Kun , Xia Yu , Wu Qian , Yin Miao , Zhao Hong , Chen Xi-wen 
Published: January 2025

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen that has caused severe economic losses in the swine industry. Screening key host immune-related genetic factors in the porcine alveolar macrophages (PAMs) is critical to improve the anti-virial ability in pigs.MethodsIn this study, an in vivo model was set to evaluate the anti-PRRSV effect of tylvalosin tartrates. Then, strand-specific RNA-sequencing (ssRNA-seq) and miRNA-sequencing (miRNA-seq) were carried out to profile the whole transcriptome of PAMs in the negative control, PRRSV-infected, and tylvalosin tartrates-treatment group.ResultsThe ssRNA-seq identified 11740 long non-coding RNAs in PAMs. Based on our attention mechanism-improved graph convolutional network, 41.07% and 28.59% lncRNAs were predicted to be located in the nucleus and cytoplasm, respectively. The miRNA-seq revealed that tylvalosin tartrates-enhanced miRNAs might play roles in regulating angiogenesis and innate immune-related functions, and it rescued the expression of three anti-inflammation miRNAs (ssc-miR-30a-5p, ssc-miR-218-5p, and ssc-miR-218) that were downregulated due to PRRSV infection. The cytoplasmic lncRNAs enhanced by tylvalosin tartrates might form ceRNA networks with miRNAs to regulate PAM chemotaxis. While cytoplasmic lncRNAs that were rescued by tylvalosin tartrates might protect PAMs via efferocytosis-related ceRNA networks. On the other hand, the tylvalosin tartrates-rescued nuclear lncRNAs might negatively regulate T cell apoptosis and bind to key anti-inflammation factor IL37 to protect the lungs by cis- and trans-regulation.ConclusionsOur data provides a catalog of key non-coding RNAs in response to PRRSV and tylvalosin tartrates and might enrich the genetic basis for future PRRSV prevention and control.
Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis
Authors: Ma Leshi , Zhang Jing , Dai Zi , Liao Pei , Guan Jieshan , Luo Zhijie 
Published: January 2025

BackgroundRecently there has been an increasing number of studies have explored apoptosis mechanisms in lung cancer (LC). However, no researchers have conducted a bibliometric analysis of the most cited articles in this field.ObjectiveTo examine the top 100 most influential and cited publications on apoptosis in non-small cell lung cancer (NSCLC) from 2004 to 2023, summarizing research trends and key focus areas.MethodsThis study utilized the Web of Science Core Database (WOSCC) to research NSCLC apoptosis from 2004 to 2023, using keyword selection and manual screening for article searches. Bibliometrix package of R software 4.3.1 was used to generate distribution statistics for the top ten institutions, journals and authors. Citespace6.2. R6 was used to create the visualization maps for keyword co-occurrence and clustering. VOSviewer1.6.19 was used to conduct cluster analysis of publishing countries (regions), with data exported to SCImago Graphica for geographic visualization and cooperation analysis. VOSviewer1.6.19 was used to produced co-citation maps of institutions, journals, authors, and references.ResultsFrom 2004 to 2023, 13316 articles were retrieved, and the top 100 most cited were chosen. These were authored by 934 individuals from 269 institutions across 18 countries and appeared in 45 journals. Citations ranged from 150 to 1,389, with a median of 209.5. The most influential articles appeared in 2005 and 2007 (n=13). The leading countries (regions), institutions, journals and authors were identified as the United States (n=60), Harvard University (n=64), CANCER RESEARCH (n=15), SUN M and YANG JS (n=6). The top five keywords were “expression”, “activation”, “apoptosis”, “pathway” and “gefitinib”. This study indicates that enhancing apoptosis through circular RNA regulation and targeting the Nrf2 signaling pathway could become a key research focus in recent years.ConclusionApoptosis has been the subject of extensive research over many years, particularly in relation to its role in the pathogenesis, diagnosis, and treatment of NSCLC. This study aims to identify highly influential articles and forecast emerging research trends, thereby offering insights into novel therapeutic targets and strategies to overcome drug resistance. The findings are intended to serve as a valuable reference for scholars engaged in this field of study.
AIP56, an AB toxin secreted by Photobacterium damselae subsp. piscicida, has tropism for myeloid cells
Authors: Freitas Inês Lua , Macedo Maria Fátima , Oliveira Liliana , Oliveira Pedro , do Vale Ana , dos Santos Nuno M.S. 
Published: January 2025

IntroductionThe AB-type toxin AIP56 is a key virulence factor of Photobacterium damselae subsp. piscicida (Phdp), inducing apoptosis in fish immune cells. The discovery of AIP56-like and AIP56-related toxins in diverse organisms, including human-associated Vibrio strains, highlights the evolutionary conservation of this toxin family, suggesting that AIP56 and its homologs may share conserved receptors across species. These toxins have potential for biotechnological applications, such as therapeutic protein delivery and immune modulation.MethodsHerein, the cell specificity of AIP56 for immune cells was characterized. The tropism of AIP56 for cells of the sea bass, mouse and human immune system was analyzed by following toxin internalization by flow cytometry and arrival of the toxin in the cytosol by evaluating the cleavage of NF-kB p65 by western blotting.ResultsOnly a small population of sea bass neutrophils internalized AIP56, indicating that most of the neutrophilic destruction during Phdp infection and/or AIP56 intoxication does not result from the direct action of the toxin. Moreover, the cellular tropism of AIP56 for myeloid cells was observed in the three species, including its preference for macrophages. Further, mouse and human M0 and M2-like macrophages internalized more toxin than M1-like macrophages. Despite the limited interaction of lymphoid cells with AIP56, mouse B1-cells were able to internalize the toxin, possibly due to its myeloid features.ConclusionAIP56 has tropism for sea bass, mouse and human myeloid cells, with greater affinity for macrophages. This points to an evolutionary conservation of its receptor(s) and mechanism of action across species, raising the possibility that AIP56-like and -related toxins may also play a role in pathogenesis. These findings are relevant for both pathogenicity and biomedical contexts.
Proteomics and transcriptomics combined reveal specific immunological markers in autoimmune thyroid disease
Authors: Chen Xia , Chen Hui 
Published: January 2025

ObjectiveThe pathogenesis of AITD remains unclear to date. This study employs a combination of proteomics and transcriptomics analysis to identify and validate specific immune response markers in patients with hyperthyroidism and hypothyroidism, thereby providing a scientific basis for the clinical diagnosis and treatment of AITD.MethodsBy collecting serum and whole blood tissue samples from patients with hyperthyroidism, hypothyroidism, and healthy controls, this study utilizes a combination of transcriptomics and proteomics to analyze changes in immune-related signaling molecules in patients. Specific biomarkers were identified, and the ELISA method was employed to determine the expression levels of these clinical markers and their correlation with clinical features of the patients, ultimately establishing a predictive model.ResultsTranscriptomic and proteomic analyses were conducted to identify differentially expressed genes and proteins in patients with hyperthyroidism and hypothyroidism compared to healthy controls. Enrichment analysis revealed that these differentially expressed genes and proteins are primarily associated with immune function, antigen-antibody binding, and alterations in immune cells. Through the combined analysis of transcriptomics and proteomics, key genes IGHG3, ISG15, and ZNF683 were identified. ELISA results from clinical patient serum samples indicated that the levels of IGHG3 were significantly higher in both the hyperthyroid and hypothyroid groups compared to the control group (P&lt;0.05). Additionally, the serum levels of ISG15 in the hyperthyroid group were greater than those in both the control and hypothyroid groups (P&lt;0.05), while the serum levels of ZNF683 in the hypothyroid group exceeded those in the control and hyperthyroid groups (P&lt;0.05). Furthermore, all three biomarkers correlated with the thyroid function of the patients. Prediction models for hyperthyroid and hypothyroid patients were constructed using IGHG3, ISG15, and ZNF683, demonstrating good performance metrics and decision effect.ConclusionIn patients with hyperthyroidism and hypothyroidism, significant changes primarily occur in immune function and immune cells when compared to healthy individuals. Key signaling molecules were identified: ISG15 for hyperthyroidism, ZNF683 for hypothyroidism, and IGHG3 common to both conditions. These findings provide new biomarkers for the diagnosis and monitoring of clinical patients, thereby offering a scientific basis for research on AITD and personalized treatment approaches.
MiR-4298 and lncKRTAP5-6-3 regulated Cathepsin D expression through ERK-MAPK signaling pathway in chronic UVB-damaged HaCaT cells
Authors: Chen Xinling , Zhou Feng , Lin Yao , Xia Yue , Zhang Jie , Hou Wenyi , Sun Yu , Lai Wei , Zheng Yue 
Published: January 2025

ObjectiveMiRNAs and lncRNAs are important regulators in the process of skin photoaging. In this study, we investigated the expression changes and interactions between miR4298 and lncKRTAP5-6-3 in chronically UVB-damaged human keratinocyte cell line (HaCaT) cells and explored miR4298-MAPK/ERK signaling pathway-Cathepsin D-lncKRTAP5-6-3 mechanisms in photoaging cells.MethodsHaCaT cells were irradiated with 12 mJ/cm2 UVB once a day for 7 days. miR-4298 mimics and miR-4298 inhibitors were transfected into HaCaT cells by lipo3000 transfection reagent, and the HaCaT cells were divided into three groups: blank control group; UVB-damaged group; and UVB damage+miR-4298 regulation (overexpression or inhibition) group. The expression levels of miR4298 and lncKRTAP5-6-3 were quantitatively analyzed using RT-PCR, while the expression of Cathepsin D and MAPK/ERK signaling pathway proteins was detected using Western blot.ResultsAfter 7 consecutive days of UVB irradiation, the expression of miR-4298 decreased by 0.64 ± 0.06 (P &lt; 0.001) compared to the un-irradiated HaCaT cells, and the expression of the KRTAP5-6-3 decreased by 0.80 ± 0.13 (P &lt; 0.001) compared to the control group. The expression of p-ERK signaling was increased by 0.9437 ± 0.1186 (P &lt; 0.0001), and Cathepsin D was decreased by 0.6163 ± 0.075 (P &lt; 0.0001). In HaCaT cells transfected with miR-4298 mimics and then irradiated by UVB for 7 days, the expression of lncKRTAP5-6-3 was increased to 0.5114 ± 0.1438 (P &lt; 0.05)-fold, and the phosphorylation level of ERK signaling was decreased by 0.3880 ± 0.1185 (P &lt; 0.01), while Cathepsin D expression was increased by 0.2617 ± 0.0749 (P &lt; 0.0001) compared to the UVB-damaged group. In HaCaT cells transfected with miR-4298 inhibitors and then irradiated by UVB for 7 days, lncKRTAP5-6-3 was decreased by 0.1697 ± 0.1383, the phosphorylation level of ERK signaling was increased by 1.096 ± 0.7836 (P &lt; 0.05), while Cathepsin D expression was decreased by 0.05197 ± 0.24827 compared to the UVB-damaged group.ConclusionThe synergistic effects of miR4298 and lncKRTAP5-6-3 play important roles in chronic UVB-damaged HaCaT cells by regulating the MAPK/ERK signaling pathway and Cathepsin D expression. This study presents novel targets for intervening in chronic ultraviolet damage (photoaging) skin and UV-related dermatoses.
VV-ECMO adjuvant therapy for Leptospira complicated with H1N1 infection: a case report
Authors: Zhang YuChou , Yin MingJing , Wen HanChun 
Published: January 2025

BackgroundLeptospirosis is an acute infectious disease that occurs by infection, progresses rapidly, and has a high mortality rate, with an estimated 1.2 million new cases and nearly 59,000 deaths each year. Due to its diverse clinical manifestations, diagnosis is often delayed. Therefore, it is necessary to pay attention to its clinical manifestations, diagnostic techniques, and treatment methods.Case reportA 51-year-old male patient from the Han ethnic group experienced fever, chills, headache, and overall fatigue after being exposed to rain, followed by yellowing of the skin and worsening of breathing difficulties. Metagenomic next-generation sequencing (mNGS) indicates infection with leptospirosis and influenza A. After 5 days of treatment with venovenous extracorporeal membrane oxygenation (VV-ECMO), Penicillium, and Oseltamivir, the condition improved.ConclusionLeptospirosis improves with VV-ECMO support and anti-infective treatment with penicillin and oseltamivir. VV-ECMO provides a therapeutic time window for rescue, and mNGS lays a foundation for early detection of etiology of leptospirosis.
Effect of invasive acupuncture on awakening quality after general anesthesia: systematic review and meta-analysis
Authors: Bu Fan-dong , Si Shang-kun , Zhang Dong-bin , Chi Yong-liang 
Published: January 2025

BackgroundThe process of waking up from general anesthesia is still not well understood, and recovery issues such as delayed awakening, agitation, postoperative cognitive dysfunction, continue to be a challenge for anesthesiologists. Currently, the treatment of these complications is mainly achieved through the antagonistic action of specific drugs, but sometimes the antagonistic drugs are not as effective as they should be and can add to the financial burden of the patient. Acupuncture, a common treatment in Traditional Chinese Medicine, is widely used around surgery. However, there is no enough evidence to show it improves recovery after anesthesia. To explore this, we reviewed relevant randomized trials and conducted a meta-analysis.ObjectiveThis systematic review was conducted to explore the effect of perioperative application of invasive acupuncture on the quality of postoperative awakening after general anesthesia.MethodsBy searching PubMed, Embase, Cochrane Clinical Trials Center, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wanfang Medical Database, Weipu Database, to include randomized controlled trials of invasive acupuncture applied perioperatively. Search is limited from the build-up of the database to March 2022. The statistical analysis was conducted using RevMan 5.3. Quality assessment of the included research literature using Cochrane-recommended risk of bias assessment tool.Results18 randomized controlled trials were included with 1,127 patients. 565 patients in invasive acupuncture intervention group, 562 patients in control group. Results showed that invasive acupuncture group had a shorter eye opening time than control group (MD = −6.42, 95% CI [−8.17, −4.66], p &lt; 0.001), shorter extubation times (MD = -5.84, 95% CI [−8.12, −3.56], p &lt; 0.001), lower MAP at extubation (MD = −18.54, 95% CI [−22.69, −14.39], p &lt; 0.001), lower HR at extubation (MD = −14.85, 95% CI [−23.90, −5.81], p &lt; 0.001). No statistical difference in the occurrence of POCD (OR = 0.56, 95% CI [0.28, 1.11], p = 0.10) and postoperative agitation (OR = 0.42, 95% CI [0.11, 1.65], p = 0.21).Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42023410260.