bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging human coronary cholesterol/urate crystals with cross-polarized micro-optical coherence tomography
Authors: Nishimiya Kensuke , Sharma Gargi , Singh Kanwarpal , Ahsen Osman O. , Gardecki Joseph A. , Tearney Guillermo J.
Published: October 2024

Introduction

Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-µOCT) for visualizing individual birefringent crystals in human coronary arteries.

Methods and results

Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-µOCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-µOCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-µOCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (p < 0.05), and thus were MSU. CP-µOCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 (x) × 500 (y) × 400 (z) µm]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-µOCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-µOCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (R = 0.98, p < 0.01), and with histology-derived intimal thickening (R = 0.51, p < 0.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (p < 0.05).

Discussion

These results demonstrate a significant increase in CP-µOCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.
Screening of m6A-associated ferroptosis-related genes in atherosclerosis based on WGCNA
Authors: Jiang Meiling , Zhao Weidong , Wu Liyong , Zhu Guofu
Published: October 2024

Background

N6-methyladenosine (m6A) has been shown to mediate ferroptosis but its role in atherosclerosis (AS) is unclear.

Methods

Differentially expressed m6A-associated ferroptosis-related genes (DE-m6A-Ferr-RGs) were obtained using differential expression analysis and Pearson correlation analysis. Weighted gene co-expression network analysis (WGCNA) was also performed. The intersection of the module genes and the DE-m6A-Ferr-RGs were recorded as candidate m6A-Ferr-related signature genes. Finally, the m6A-Ferr-related signature genes were screened using least absolute shrinkage and selection operator (LASSO) analysis. Expression validation, receiver operating characteristic ( mapping, and immune correlation analysis were also performed based on the m6A-Ferr-related signature genes. The expression of m6A-Ferr-related signature genes was further validated using a real-time polymerase chain reaction (RT-qPCR).

Results

In total, 6,167 differentially expressed genes were intersected with 24 m6A- and 259 ferroptosis-related genes, respectively, resulting in 113 DE-m6A-Ferr-RGs obtained using Pearson’s correlation analysis. The module genes obtained from the WGCNA and the 113 DE-m6A-Ferr-RGs were intersected to obtain 48 candidate m6A-Ferr-related signature genes. LASSO analysis was performed and six m6A-Ferr-related signature genes were screened. In addition, the area under the curve values of all six m6A-Ferr-related signature genes were greater than 0.7, indicating that they had potential diagnostic value. Furthermore, the RT-qPCR results revealed that the expression of SLC3A2, NOX4, and CDO1 was consistent with the transcriptome level. Moreover, there was a significant difference in two types of immune cells between the AS and control groups. Naive B cells, CD8+ T cells, regulatory T cells, and activated natural killer cells were positively correlated with CDO1 and NOX4 but negatively correlated with ATG7, CYBB, and SLC3A2.

Conclusion

In total, three m6A-Ferr-related signature genes (NOX4, CDO1, and SLC3A2) were obtained through a series of bioinformatics analyses and an RT-qPCR.
Technoference in infant feeding: the impact of maternal digital media use during breastfeeding on maternal attention and mother-infant interactions
Authors: Mason Emma M. , Riccabona Tyne M. , Ventura Alison K.
Published: October 2024

Introduction

Parents' sensitivity and responsiveness to their infants may be affected by the widespread availability and use of mobile devices. The present study examined the impact of maternal digital media use on maternal attention and the quality of mother-infant interaction during breastfeeding.

Methods

Mothers and infants (n = 25 dyads) participated in a within-subject experiment. Mothers breastfed their infants under one experimental and one control condition, counterbalanced across two laboratory visits. During the Digital Media condition, mothers watched a television show on a tablet. During the Control condition, mothers listened to classical music at ambient levels. Video records were later coded to assess maternal attention to the infant, tablet, or elsewhere and evaluate the quality of mother-infant interaction.

Results

There were more disruptions in maternal attention to the infant during the Digital Media (M = 3.7, S.E. = 0.2 per minute) vs. Control condition (M = 1.7, S.E. = 0.2 per minute, p < 0.001). The proportion of the meal duration mothers spent focused on their infant was significantly lower during the Digital Media (M = 52.5%, S.E. = 3.9) vs. Control condition (M = 83.9%, S.E. = 4.0%, p < 0.001). Lower maternal attention to the infant was associated with lower maternal sensitivity to cues (p = 0.03) and cognitive growth fostering (p = 0.002), as well as lower infant clarity of cues (p = 0.001). Lower maternal attention was also associated with less socioemotional growth fostering (p < 0.001) and lower infant responsiveness to the mother (p < 0.001) regardless of whether digital media was present or absent, but during the Digital Media condition, mothers engaged in more socioemotional growth fostering (p = 0.004) and infants were more responsive to mothers (p = 0.03).

Discussion

The presence of digital media during infant feeding led to more interruptions to mothers' attention to their infants and the time mothers spent focused on digital media displaced time spent focused on their infants. The degree to which mothers were attentive to their infants vs. digital media was a more important predictor of most aspects of interaction quality than the mere presence of digital media.
Roles of helminth extracellular vesicle-derived let-7 in host–parasite crosstalk
Authors: Zhong Haoran , Guan Guiquan , Jin Yamei
Published: October 2024

Helminth infections are a major public health problem as they can cause long-term chronic infections in their hosts for which there is no effective vaccine. During the long-term interaction between helminths and their hosts, helminth-derived extracellular vesicles (EVs) can participate in host immunomodulatory processes by secreting bioactive molecules (BMAs). Growing data suggests that microRNAs (miRNAs) in helminth EVs have a significant impact on the host’s immune system. The let-7 family is highly conserved among helminth EVs and highly homologous in the host, and its function in host–parasite crosstalk may reflect active selection for compatibility with the host miRNA machinery. In-depth studies targeting this aspect may better elucidate the mechanism of parasite-host interactions. Hence, this review summarizes the current studies on the cross-species involvement of helminth EV-derived let-7 in host immune regulation and discusses the barriers to related research and potential applications of helminth EVs.
Successful eculizumab treatment as an adjunctive therapy to desensitization in ABO-incompatible living donor kidney transplantation and its molecular phenotypes
Authors: Heo Ga Young , Jung Minsun , Piao Honglin , Kim Hyun Jeong , Kim Hyung Woo , Lee Juhan , Huh Kyu Ha , Kim Beom Seok , Yang Jaeseok
Published: October 2024

Introduction

ABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi KT. However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR.

Methods

Eculizumab treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively.

Results

The initial titers of anti-ABO antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells.

Conclusions

Short-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.
Cuproptosis-related lncRNAs emerge as a novel signature for predicting prognosis in prostate carcinoma and functional experimental validation
Authors: Lu Yangbai- , Wu Jinfeng- , Li Xianzhe , Leng Qu- , Tan Jian- , Huang Hongxing- , Zhong Rui- , Chen Zhenjie- , Zhang Yongxin-
Published: October 2024

Background

Prostate cancer (PCa) is one of the most common malignancies of the urinary system. Cuproptosis, a newly discovered form of cell death. The relationship between cuproptosis-related long non-coding RNAs (ClncRNAs) related to PCa and prognosis remains unclear. This study aimed to explore the clinical significance of novel ClncRNAs in the prognostic assessment of PCa.

Methods

ClncRNAs and differentially expressed mRNAs linked to these ClncRNAs were identified using Pearson’s correlation and differential expression analyses. A prognostic signature (risk score) comprising three ClncRNAs was established based on multivariable Cox regression analysis. The predictive performance of this ClncRNAs signature was validated using receiver operating characteristic curves and nomograms. Finally, further in vitro cell experiments were conducted for validation, including quantitative polymerase chain reaction (qPCR), western blot (WB), cell proliferation assays, cell migration assays, cell invasion assays, apoptosis, and cell cycle analysis.

Results

We constructed a prognostic signature of ClncRNAs for PCa comprising three key differentially expressed ClncRNAs(AC010896-1, AC016394-2, and SNHG9). Multivariable Cox regression analysis indicated that clinical staging and risk scores of the ClncRNAs signature were independent prognostic factors for PCa. Compared to other clinical features, the ClncRNAs signature exhibited higher diagnostic efficiency and performed well in predicting the 1-, 3-, and 5-year progression-free intervals (PFIs) for PCa. Notably, in terms of immune activity, PCa patients with high-risk scores exhibited higher tumor mutational burden (TMB) levels, while their Tumor Immune Dysfunction and Exclusion (TIDE) scores were lower than those of PCa patients with low-risk scores. Additionally, in vitro cellular functional experiments, we knocked down SNHG9 that is the most significantly differentially expressed ClncRNA among the three key ClncRNAs. SNHG9 knockdown resulted in a significant increase in G1 phase cells and a decrease in S and G2 phases, indicating inhibition of DNA synthesis and cell cycle progression. Colony formation assays showed reduced clonogenic ability, with fewer and smaller colonies. Western blot analysis revealed the upregulation of the key cuproptosis-related mRNAs FDX1 and DLST. These findings suggested that SNHG9 promotes PCa cell proliferation, migration, and invasion.

Conclusion

Building on the three ClncRNAs, we identified a novel prognostic signature of PCa. The ClncRNA SNHG9 can promote PCa cell proliferation, migration, and invasion.
Genetically predicted plasma metabolites mediate the causal relationship between gut microbiota and primary immune thrombocytopenia (ITP)
Authors: Hong Yang , Zhang Cuilin , Shen Kai , Dong Xiaoqing , Chen Bing
Published: October 2024

Background

Primary immune thrombocytopenia (ITP) is an immune-mediated hematologic disorder characterized by a reduction in platelet count, increasing the risk of bleeding. Recent studies have indicated a close association between alterations in gut microbiota and the development of ITP. However, the mechanisms by which gut microbiota influence the occurrence and progression of ITP through plasma metabolites remain poorly understood. Evidence suggests extensive interactions between gut microbiota and plasma metabolites, implying a potential role for gut microbiota in influencing ITP through alterations in plasma metabolites, which requires further investigation.

Methods

In this study, summarized GWAS data (including 211 gut microbiota taxa, 1,400 plasma metabolites or ratios, and an ITP patient cohort) were retrieved from the MiBioGen and GWAS Catalog databases. Using a two-sample Mendelian randomization (MR) approach, we screened gut microbiota and plasma metabolites potentially causally related to ITP. We further identified plasma metabolites serving as mediators through which gut microbiota affect ITP and calculated the strength of the mediation effect. To ensure result stability, we primarily used the inverse variance weighted (IVW) method as the main judgment index. We also utilized MR Egger and inverse variance weighted methods to detect heterogeneity in the results, and employed MR-Egger and MR-PRESSO methods to assess the presence of pleiotropy.

Results

Though two-sample MR analysis, 8 gut microbiota taxa were found to have causal relationships with ITP. After excluding six plasma metabolites with pleiotropy, 39 plasma metabolites were found to be causally related to ITP (P < 0.05). Eleven plasma metabolites were identified as having causal relationships between gut microbiota and plasma metabolites. Finally, using the delta method, it was calculated that Sphingomyelin levels (8.0%, 95%CI: 0.9% to 11.5%, P = 0.047) and Glucose-to-mannose ratio (6.5%, 95%CI: 0.7% to 9.5%, P = 0.039) are intermediates for Intestinimonas influencing ITP, while Bilirubin (Z,Z) to etiocholanolone glucuronide ratio (5.6%, 95%CI: 4.7% to 6.9%, P = 0.043) is an intermediate for Senegalimassilia influencing ITP.

Conclusion

Gut microbiota can influence the development of ITP through changes in plasma metabolites. Sphingomyelin levels, Glucose-to-mannose ratio, and Bilirubin (Z,Z) to etiocholanolone glucuronide ratio are newly discovered intermediates through which gut microbiota influence ITP, providing potential indicators and targets for clinical diagnosis and treatment. This study highlights the intricate relationship between gut microbiota and plasma metabolites in the context of ITP, suggesting new avenues for clinical diagnosis and treatment.
Japanese encephalitis virus infection induces mitochondrial-mediated apoptosis through the proapoptotic protein BAX
Authors: Yang Ke , Li Xinran , Yang Shuqing , Zheng Yi , Cao Sanjie , Yan Qigui , Huang Xiaobo , Wen Yiping , Zhao Qin , Du Senyan , Lang Yifei , Zhao Shan , Wu Rui
Published: October 2024

The Japanese encephalitis virus (JEV), a zoonotic flavivirus, is Asia’s primary cause of viral encephalitis. JEV induces apoptosis in a variety of cells; however, the precise mechanisms underlying this apoptosis resulting from JEV infection remain to be elucidated. Our previous studies showed that the proapoptosis gene BAX may have a role in JEV proliferation. In this study, we constructed a PK-15 cell line (BAX.KO) with a knockout of the BAX gene using CRISPR/Cas9. The knockout of the BAX gene effectively inhibited the proliferation of JEV, resulting in a 39.9% decrease in viral protein levels, while BAX overexpression produced the opposite effect. We confirmed that JEV induces apoptosis of PK-15 using 4′,6-diamidino-2-phenylindole (DAPI) staining and Annexin V-FITC/PI staining. Furthermore, we found that the phosphorylation of P53 and the expression levels of BAX, NOXA, PUMA, and cleaved-caspase-3/9 were significantly upregulated after JEV infection. Moreover, we found that JEV infection not only caused mitochondrial damage, the release of mitochondrial cytochrome C (Cyt C), and the downregulation of the apoptosis-inhibiting protein BCL-2 but also reduced the mitochondrial membrane potential (MOMP) and the accumulation of intracellular reactive oxygen species (ROS). These factors collectively encourage the activation of the mitochondrial apoptosis pathway. In contrast, BAX gene knockout significantly reduces the apoptotic changes caused by JEV infection. Treatment with the caspase3 inhibitor attenuated JEV-induced viral proliferation and release, leading to a decrease in viral protein levels of 46% in PK-15 cells and 30% in BAX.KO cells. In conclusion, this study clarified the molecular mechanisms of JEV-induced apoptosis and provided a theoretical basis for revealing the pathogenic mechanisms of JEV infection.
Effects of plastic film mulching on soil microbial carbon metabolic activity and functional diversity at different maize growth stages in cool, semi-arid regions
Authors: Kong Meng , Huang Ming-Jing , Zhang Zhi-Xian , Long Jiang , Siddique Kadambot H. M. , Zhang Dong-Mei
Published: October 2024

Introduction

Plastic film mulching has been widely used to enhance soil hydrothermal conditions and increase crop yields in cool, semi-arid areas. However, its impact on soil microbial carbon metabolic activity and functional diversity during plant growth remains unclear despite their important roles in nutrient cycling and soil quality evaluation.

Methods

This study used the Biolog EcoPlate technique to investigate the dynamics and driving factors of soil microbial carbon metabolic activity and functional diversity at different maize growth stages following plastic film mulching.

Results and discussion

The results revealed that film mulching significantly increased microbial carbon metabolic activities [represented by average well color development (AWCD)] by 300% at the seedling stage and by 26.8% at maturity but decreased it by 47.4% at the flowering stage compared to the control (without mulching). A similar trend was observed for the microbial functional diversity index. Redundancy analysis identified soil moisture (SM), soil temperature (ST), dissolved organic carbon (DOC), microbial biomass carbon (MBC), and bacteria amounts as the primary factors influencing changes in soil microbial carbon source utilization. The mulch treatment significantly increased SM at all growth stages, while its warming effect disappeared at the flowering stage. Soil DOC, MBC, and bacterial populations were notably higher under mulching at the seedling and maturity stages but lower at the flowering stage. Pearson correlation analysis showed that changes in SM, ST, DOC, MBC, and bacterial populations positively correlated with the utilization of all carbon source classes, AWCD, and functional diversity indexes after film mulching. Furthermore, maize grain yield and water use efficiency increased by 142 and 129%, respectively, following film mulching. In conclusion, plastic film mulching enhanced soil microbial carbon metabolic activity and functional diversity at the seedling and maturity stages, improving crop yields in cool, semi-arid areas. Furthermore, the decrease in soil carbon metabolic capacity at flowering stage highlights that supplementing soil carbon sources should be considered after continuous film mulching to sustain or enhance farmland productivity and soil quality.
A severity comparison of leukoaraiosis in ischemic and hemorrhagic stroke: a retrospective study
Authors: Søfteland Bendik , Leto Nedim , Næss Halvor
Published: October 2024

Introduction

Leukoaraiosis (LA) is a common neuroradiological finding in patients suffering from stroke. Cerebral small-vessel disease (SVD) is one of the primary causes of both ischemic stroke and hemorrhagic stroke (intracerebral hemorrhage, ICH) and the development of LA. Significant evidence that LA predicts the risk of functional dependency and mortality exists. However, studies examining the difference in LA severity between ischemic stroke and hemorrhagic stroke are lacking. We therefore aimed to compare the severity and abundance of LA in the two stroke subgroups.

Methods

All patients admitted to the Department of Neurology, Haukeland University Hospital, with an ischemic stroke and intracerebral hemorrhagic (ICH) stroke diagnosed between 2006 and 2020 were included in the study. We collected patient data on risk factors and clinical and radiological findings and outcomes from our local stroke registry. The presence and severity of LA were assessed using the Fazekas score based on CT imaging. We evaluated the outcome using the modified Rankin Score (mRS) 7 days post-stroke.

Results

A total of 5,084 patients were included in our analyses: 4437 (87%) with ischemic stroke and 647 (13%) with ICH. LA was present in 2476 (45%) patients. In our ordinal logistic regression model, adjusting for age, sex, known hypertension, known diabetes mellitus, and smoking, LA was more severe and more abundant in ICH patients compared to ischemic stroke patients (Fazekas score: 1, OR: 1.54; Fazekas score: 2, OR: 1.88; and Fazekas score: 3, OR 2.13; p < 0.001). Increasing severity of LA was associated with worse functional outcomes in both groups (ischemic stroke, OR: 1.49; p < 0.001 and ICH, OR: 1.36; p < 0.025).

Conclusion

In this study, LA was more severe and abundant in patients with ICH.
Model of superior semicircular canal dehiscence: asymmetrical vestibular dysfunction induces reversible balance impairment
Authors: Hong Sean S. , Wackym P. Ashley , Murphy Damian J. , Peci Eran , Kiel Matthew Y. , Tucker Aaron , Carayannopoulos Nicolas L. , Chandrasekar Shrivaishnavi C. , Suresh Nikhil , Utku Umut A. , Yao Justin D. , Mowery Todd M.
Published: October 2024

Background

Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition. A feature that is unique in this model is that spontaneous resurfacing of the dehiscence occurs via osteoneogenesis without a subsequent intervention. In this study, we completed our assessment of this model to include reversible asymmetrical vestibular impairments that interfere with balance.

Methods

Adult Mongolian gerbils (N = 6) were trained to complete a balance beam task. They were also trained to perform a Rotarod task. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Balance beam testing recommenced at postoperative day 6 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out.

Results

Behavioral comparison of preoperative and postoperative performance show a significant decrease in Rotarod performance, increased rates of falling, and an increase in time to cross the balance beam. Impairments were the most significant at postoperative day 7 with a return toward preoperative performance by postoperative day 14. This behavioral impairment was correlated with residual impairments to auditory thresholds and vestibular myogenic amplitudes at postoperative day 14.

Conclusion

These results confirm that aberrant asymmetric vestibular output in our model of SSCD results in reversible balance impairments. The level of these behavioral impairments is directly correlated with severity of the vestibular dysfunction as we have previously reported for peripheral ear physiology and cognition.
Initiation response, maximized therapeutic efficacy, and post-treatment effects of biological targeted therapies in myasthenia gravis: a systematic review and network meta-analysis
Authors: Zhong Huahua , Li Zhijun , Li Xicheng , Wu Zongtai , Yan Chong , Luo Sushan , Zhao Chongbo
Published: October 2024

Background

As targeted drug development in myasthenia gravis (MG) continues to advance, it is important to compare the efficacy of these drugs for better clinical decision-making. However, due to the varied regimens and dosages used in clinical trials for different drugs, a standardized comparison between them is necessary.

Methods

This study enrolled participants in phase II and III trials of innovative targeted drugs for MG. The primary outcome was the change in Quantitative Myasthenia Gravis score (MG-QMG) from baseline. The efficacy of all drugs at four time points was separately analyzed at four time points: initiation 1 week, initiation 4 weeks, maximized response, and post last dose 4 weeks. A network meta-analysis was conducted to compare the results of the different drugs.

Results

A total of 9 drugs, including Efgartigimod, Rozanolixizumab, Batoclimab, Eculizumab, Belimumab, Zilucoplan, Ravulizumab, Nipocalimab, Rituximab, derived from 12 studies were analyzed. At the initiation 1-week time point, three drugs exhibited significant improvement compared to the placebo effect: Efgartigimod, Zilucoplan, Rozanolixizumab. At the initiation 4-week time point, four drugs showed significant improvement compared to the placebo effect: Efgartigimod, Rozanolixizumab, Batoclimab, Zilucoplan. At the maximized response time point, six drugs achieved significant improvement compared to the placebo effect: Efgartigimod, Rozanolixizumab, Batoclimab, Eculizumab, Zilucoplan, Ravulizumab. At the post last dose 4-week point, all drugs statistically showed no significant difference from the placebo.

Conclusion

Although the MG subtypes were not consistent across trials, within the regimen design of each trial, neonatal Fc receptor inhibitors—represented by Efgartigimod, Rozanolixizumab, and Batoclimab—exhibited the most effective response rates when compared to complement and B-cell inhibitor drugs.
Krill oil supplementation in vivo promotes increased fuel metabolism and protein synthesis in cultured human skeletal muscle cells
Authors: Katare Parmeshwar B. , Dalmao-Fernandez Andrea , Mengeste Abel M. , Navabakbar Farnaz , Hamarsland Håvard , Ellefsen Stian , Berge Rolf K. , Bakke Hege G. , Nyman Tuula Anneli , Kase Eili Tranheim , Rustan Arild C. , Thoresen G. Hege
Published: October 2024

Introduction

Krill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in human skeletal muscle cells.

Methods

Skeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. The functional data were combined with proteomic and transcriptomic analyses.

Results

In vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism in myotubes, enhancing energy substrate utilization. Transcriptomic analysis comparing myotubes obtained before and after krill oil supplementation identified differentially expressed genes associated with e.g., glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g., LDL-receptor in myotubes obtained after the krill oil intervention.

Conclusion

These findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.
Applications of artificial intelligence in digital pathology for gastric cancer
Authors: Chen Sheng , Ding Ping’an , Guo Honghai , Meng Lingjiao , Zhao Qun , Li Cong
Published: October 2024

Gastric cancer is one of the most common cancers and is one of the leading causes of cancer-related deaths in worldwide. Early diagnosis and treatment are essential for a positive outcome. The integration of artificial intelligence in the pathology field is increasingly widespread, including histopathological images analysis. In recent years, the application of digital pathology technology emerged as a potential solution to enhance the understanding and management of gastric cancer. Through sophisticated image analysis algorithms, artificial intelligence technologies facilitate the accuracy and sensitivity of gastric cancer diagnosis and treatment and personalized therapeutic strategies. This review aims to evaluate the current landscape and future potential of artificial intelligence in transforming gastric cancer pathology, so as to provide ideas for future research.
Response to furmonertinib in a patient with non-small cell lung cancer harboring HER2 exon 21 insertion mutation: a case report
Authors: Ni Chunxiao , Zhang Ling , Yu Xin , Pang Yu , Xu Jiaju
Published: October 2024

Background

This is the first case report describing a patient with non-small cell lung cancer (NSCLC) harboring two rare human epidermal growth factor receptor 2 (HER2) exon 21 insertion mutations, who responded to furmonertinib treatment. Furmonertinib maybe one effective and economical treatment for NSCLC patients harboring HER2 mutations with minor side effects.

Case description

We present a case report of a 49-year-old female diagnosed with stage IV lung adenocarcinoma who complained of irritating dry cough symptoms followed by chest tightness. Firstly, we describe the patient’s treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient’s fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed. After that, comprehensive genomic profiling revealed two HER2 exon 21 insertion mutations. Subsequently, the patient received targeted therapy with furmonertinib and achieved 11 months of progression-free survival. The patient received pyrrotinib therapy for 2 months after disease progression, but the disease continued to progress. In October 2023, the patient received therapy with furmonertinib again, and a month later, the disease went into partial remission. However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023.

Conclusion

Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.
Meta-analysis of the diagnostic value of exosomal microRNAs in renal cell carcinoma
Authors: Li Qingru , Tian Jing , Chen Cuiqing , Liu Hong , Li Binyi
Published: October 2024

Aim

This meta-analysis aims to evaluate the potential of exosomal microRNAs(Exo-miRs) as diagnostic biomarkers for renal cell carcinoma(RCC).

Methods

Clinical studies reporting the use of Exo-miRs in the diagnosis of RCC were retrieved from PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, VIP, and Chinese Biomedical Literature Database (SinoMed). After relevant data were screened and extracted, the quality of the included studies was assessed using the QUADAS-2 tool. The Meta-disc (version 1.4) software was used to analyze the heterogeneity of threshold/non-threshold effects in the included studies. The Stata MP (version 16.0) software was used to calculate sensitivity(Sen), specificity(Spe), positive likelihood ratio(+LR), negative likelihood ratio(-LR), area under the curve(AUC), diagnostic odds ratio(DOR), and publication bias.

Results

A total of 11 studies were included in this meta-analysis. Spearman correlation coefficient was 0.319 (P = 0.075; >0.05), indicating no threshold effects. The pooled Sen, Spe, +LR, -LR, DOR, and AUC were 0.73 (95% CI, 0.68–0.78), 0.81 (95% CI, 0.76–0.85), 3.80 (95% CI, 3.02–4.77), 0.33 (95% CI, 0.28–0.40), 11.48 (95% CI, 8.27–15.95), and 0.84 (95% CI, 0.80–0.87), respectively. No publication bias was detected among the included studies.

Conclusion

The expression of Exo-miRs plays an important role in the diagnosis of RCC. However, owing to the limited number of included studies and heterogeneity among them, further clinical research is necessary to verify the findings of this meta-analysis.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445956.
Effectiveness of partial splenic embolization in colorectal cancer patients with chemotherapy-induced thrombocytopenia: results of a single institution retrospective study
Authors: Li Dan , Peng Tao , Wu Ke-tong , Huang Yu-ting , Liu Yang , Wan Yuan , Zhang Bo
Published: October 2024

Objective

To evaluate the safety and efficacy of partial splenic embolization (PSE) in treating chemotherapy-induced thrombocytopenia (CIT) in patients with colorectal cancer who failed to respond to platelet growth factor therapy.

Methods

56 patients who underwent PSE were retrospectively analyzed. Based on the inclusion and the exclusion criteria, 29 patients were eligible for the study, of whom one underwent twice PSE procedures due to recurrent thrombocytopenia. The clinical characteristics were retrospectively analyzed with respect to efficacy, safety and outcome.

Results

60.0% of patients restarted antineoplastic therapy after PSE. There was a positive correlation between difference value of platelet count and embolization material size (Eta Squared = 0.252, p < 0.05). The correlation between the absolute volume of spleen embolized and postoperative complications was analyzed, with a statistically significant result (p < 0.001). The mean preoperative spleen volume, the preoperative platelet count, postoperative platelet count and difference value of platelet count in the non-cirrhotic group were larger than those in the cirrhotic group (p < 0.001). The mean overall survival was 47.7 ± 7.7 months.

Conclusion

PSE is safe and effective in the treatment of CIT patients with colorectal cancer. The larger the embolized particle, the more platelets grew. The severity of complication was also positively correlated with the absolute volume of spleen embolized. Therefore, large particle embolization materials can be used to improve the efficacy of PSE and reduce complications. For CIT patients with cirrhosis, PSE was less effective in improving platelet count than those without cirrhosis.
Ultrasound findings of ovarian intravenous leiomyomatosis: a case report
Authors: Li Jin , Luo Le
Published: October 2024

Intravenous leiomyomatosis (IVL), an abnormal growth pattern of uterine leiomyomas, is a rare tumor characterized by masses of smooth muscle cells appearing histologically benign and proliferating within the blood vessels but not invading the tissue. Currently, there have been limited reports of early cases of IVL, and the imaging characteristics of IVL remain uncertain, resulting in frequent misdiagnosis prior to surgery. The present study utilized a case of early IVL detected through conventional ultrasound and subsequently confirmed via contrast-enhanced ultrasound (CEUS) to further investigate ultrasound’s diagnostic efficacy for early IVL detection. Here, a case of a 49-year-old woman was reported who presented with uterine leiomyoma and an echogenic mass in the left adnexal region on physical examination. Subsequent transvaginal CEUS examination revealed a left ovarian venous leiomyoma. The patient underwent resection of tumors in the uterus, bilateral ovaries, and left ovarian vein under general anesthesia. A venous plexus was identified above the left broad ligament close to the left ovary, and a myoma-like growth was detected in the posterior uterine wall during the operational procedure. Reports on pathology and immunohistochemistry verified leiomyomatosis with fatty metaplasia in the left broad ligament and uterine wall vein. The prognosis of patients with IVL is determined based on the appropriate surgical methods and the timely diagnosis of the condition. In this case, conventional ultrasound aided in the early identification of IVL, which was later verified by a CEUS examination, resulting in a successful surgical treatment. This example highlights the importance of ultrasound technology in diagnosing this uncommon condition and presents a new method for preoperative detection of IVL.
Fluid deresuscitation in critically ill children: comparing perspectives of intensivists and nephrologists
Authors: Braun Chloe G. , Askenazi David J. , Neyra Javier A. , Prabhakaran Priya , Rahman A. K. M. Fazlur , Webb Tennille N. , Odum James D.
Published: October 2024

Introduction

Fluid accumulation, presently defined as a pathologic state of overhydration/volume overload associated with clinical impact, is common and associated with worse outcomes. At times, deresuscitation, the active removal of fluid via diuretics or ultrafiltration, is necessary. There is no consensus regarding deresuscitation in children admitted to the pediatric intensive care unit. Little is known regarding perceptions and practices among pediatric intensivists and nephrologists regarding fluid provision and deresuscitation.

Methods

Cross-sectional electronic survey of pediatric nephrologists and intensivists from academic societies in the United States designed to better understand fluid management between disciplines. A clinical vignette was used to characterize the perceptions of optimal timing and method of deresuscitation initiation at four timepoints that correspond to different stages of shock.

Results

In total, 179 respondents (140 intensivists, 39 nephrologists) completed the survey. Most 75.4% (135/179) providers believe discussing fluid balance and initiating fluid deresuscitation in pediatric intensive care unit (PICU) patients is “very important”. The first clinical vignette time point (corresponding to resuscitation phase of early shock) had the most dissimilarity between intensivists and nephrologists (p = 0.01) with regards to initiation of deresuscitation. However, providers demonstrated increasing agreement in their responses to initiate deresuscitation as the clinical vignette progressed. Compared to intensivists, nephrologists were more likely to choose “dialysis or ultrafiltration” as a deresuscitation method during the optimization [10.3 vs. 2.9% (p = 0.07)], stabilization [18.0% vs. 3.6% (p < 0.01)], and evacuation [48.7% vs. 23.6% (p < 0.01)] phases of shock. Conversely, intensivists were more likely to utilize scheduled diuretics than nephrologists [47.1% vs. 28.2% (p = 0.04)] later on in the patient course.

Discussion

Most physicians believe that discussing fluid balance and deresuscitation is important. Nevertheless, when to initiate deresuscitation and how to accomplish it differed between nephrologist and intensivists. Widely understood and operationalizable definitions, further research, and eventually evidence-based guidelines are needed to help guide care.
Machine learning methods for propensity and disease risk score estimation in high-dimensional data: a plasmode simulation and real-world data cohort analysis
Authors: Guo Yuchen , Strauss Victoria Y. , Català Martí , Jödicke Annika M. , Khalid Sara , Prieto-Alhambra Daniel
Published: October 2024

Introduction

Machine learning (ML) methods are promising and scalable alternatives for propensity score (PS) estimation, but their comparative performance in disease risk score (DRS) estimation remains unexplored.

Methods

We used real-world data comparing antihypertensive users to non-users with 69 negative control outcomes, and plasmode simulations to study the performance of ML methods in PS and DRS estimation. We conducted a cohort study using UK primary care records. Further, we conducted a plasmode simulation with synthetic treatment and outcome mimicking empirical data distributions. We compared four PS and DRS estimation methods: 1. Reference: Logistic regression including clinically chosen confounders. 2. Logistic regression with L1 regularisation (LASSO). 3. Multi-layer perceptron (MLP). 4. Extreme Gradient Boosting (XgBoost). Covariate balance, coverage of the null effect of negative control outcomes (real-world data) and bias based on the absolute difference between observed and true effects (for plasmode) were estimated. 632,201 antihypertensive users and nonusers were included.

Results

ML methods outperformed the reference method for PS estimation in some scenarios, both in terms of covariate balance and coverage/bias. Specifically, XgBoost achieved the best performance. DRS-based methods performed worse than PS in all tested scenarios.

Discussion

We found that ML methods could be reliable alternatives for PS estimation. ML-based DRS methods performed worse than PS ones, likely given the rarity of outcomes.
Adverse event profile of albumin-bound paclitaxel: a real-world pharmacovigilance analysis
Authors: Duan Yuanqiong , Wang Ying , Lu Shentao , Zeng Mei , Liu Lubin , Dai Qian , Yin Rutie
Published: October 2024

Background

Abraxane plays a crucial role in the treatment of various types of cancer, despite the considerable attention it has garnered for its adverse drug events (ADEs). Nevertheless, there is currently a significant lack of comprehensive real-world pharmacovigilance studies on the ADEs associated with Abraxane.

Methods

We conducted a retrospective analysis of ADEs associated with Abraxane using data mining from the FAERS database, analyzing data from 2005 to 2023. In a real-world setting, we quantified and visualized the signals of these ADEs using four pharmacovigilance algorithms.

Results

The FAERS database identified a total of 10,230 adverse event reports associated with Abraxane. The study revealed that Abraxane-related adverse drug events involved 27 system organ classes (SOC), with the strongest signals associated with the lymphatic and hematological systems and hepatobiliary disorders. Additionally, we identified 70 significant Preferred Terms (PT) signals, which included some critical adverse events not highlighted in the product labeling, such as cystoid macular edema. Further analysis of the timing of adverse reactions showed a median onset time of 41 days. Most adverse events (AEs) occurred within the first month of using Abraxane (43.5%), although some were still possible 1 year after treatment (3.5%). Gender-specific analysis indicated that high-risk AEs differed between females (nausea, vomiting, and erythema) and males (febrile neutropenia, disseminated intravascular coagulation, and upper gastrointestinal bleeding).

Conclusion

The examined results provide crucial recommendations for optimizing the administration of Abraxane, enhancing its effectiveness, and mitigating potential adverse effects. This knowledge will substantially facilitate the implementation of the substance in clinical settings.
Accumulation of coumaric acid is a key factor in tobacco continuous cropping obstacles
Authors: Jia Meng , Wang Xingsong , Zhu Xuanquan , Du Yu , Zhou Peng , Wang Ge , Wang Na , Bai Yuxiang
Published: October 2024

Introduction

Phenolic acids are believed to play a significant role in tobacco continuous cropping obstacles, but the strength and potential mechanisms of different phenolic acids remain unclear.

Methods

This study evaluated the allelopathic effects of six phenolic acids that exhibited cumulative effects in our previous research. Different concentrations of phenolic acids with the strongest allelopathic effects were added to potting soil to explore their impacts on tobacco growth and physiological characteristics, as well as on soil chemical properties and microbial community structure.

Results

The results showed that coumaric acid exhibited the strongest direct allelopathic effect. Exogenous coumaric acid significantly reduced soil pH and shifted the soil microbial community from bacteria-dominated to fungi-dominated. Simultaneously, the abundance of bacteria related to nutrient utilization (e.g., Flavisolibacter, Methylobacterium) and fungi related to disease resistance (e.g., Fusicolla, Clonostachys) gradually decreased, along with a reduction in soil catalase, urease, invertase, and acid phosphatase activities. Leaf MDA levels increased continuously with higher concentrations of coumaric acid, while the root resistance hormone (jasmonic acid and the jasmonate-isoleucine complex) levels show the opposite trend.

Discussion

Coumaric acid may inhibit tobacco growth by influencing the physiological processes in tobacco plants directly and the broader soil microecological balance indirectly. This study provides theoretical guidance for precise mitigation of continuous cropping obstacles in future tobacco cultivation.