bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nanotechnology-Enhanced Controlled Release Systems in Topical Therapeutics
Authors: Teklehaimanot Yohannes 
Published: December 2024

<img src=” https://s3.amazonaws.com/production.scholastica/article/127336/large/prnano_1672024ga.jpg?1733950699”> Topical and transdermal drug delivery are alternative routes for medications facing challenges like solubility, stability, and first-pass metabolism. However, conventional immediate-release dosage forms delivered topically have drawbacks, including poor penetration and high side ef-fects. Controlled-release nanoparticles offer a promising solution, improving drug permeation and providing controlled release. This review examines recent advances, challenges, and prospects of controlled-release nanoparticles for topical drug delivery. Various types of nanoparticles, including lipid nanoparticles, nanoemulsions, nanoemulgels, cubosome liposomes, poly-meric nanoparticles, solid-lipid nanoparticles, lipid-polymer hybrid nanoparticles, and nanostructured lipid carriers, carbon nanotubes, nanocomposites, and protein nanoparticles have been explored for their ability to encapsulate drugs, prolong drug release, and enhance skin permeation as well as improve therapeutic outcomes. Studies have demonstrated the effectiveness of these nanoparticles in improving sustained and controlled-release topical delivery of a wide range of drugs, including poorly soluble, low degree of skin penetration, low stability, and drugs with low bioavailability and biological products. Despite their potential benefits, challenges such as scalability, reproducibility, and safety concerns remain. Future research should ad-dress these challenges and explore novel strategies to improve efficacy and safety by converging with microneedles and 3D nanoparticles. Ultimately, controlled-release nanoparticles have the potential to revolutionize dermatological and transdermal drug delivery, leading to improved therapeutic outcomes and patient care.
Migrasome regulator TSPAN4 shapes the suppressive tumor immune microenvironment in pan-cancer
Authors: Wang Lin-jian , Xu Ruiyan , Wu Yangyang 
Published: December 2024

BackgroundMigrasomes are newly identified organelles on the retracting fibers of migrating cells, involved in releasing signaling molecules, expelling damaged mitochondria, and facilitating intercellular communication through phagocytosis. TSPAN4, a key regulator of migrasome formation, is a valuable marker for visualizing these organelles. However, its role in cancer remains unclear.MethodsWe analyzed TSPAN4 expression and its prognostic significance across multiple cancers using TCGA Pan-Cancer (PANCAN), and TCGA TARGET GTEx datasets. The relationship between TSPAN4 and tumor heterogeneity, stemness, and the immunosuppressive tumor microenvironment was explored through RNA-seq and scRNA-seq data. In addition, we examined TSPAN4's role in glioma, focusing on migrasome formation, cell proliferation, and macrophage polarization.ResultsOur analysis reveals that TSPAN4 is aberrantly expressed in various tumors, likely linked to its methylation status. It correlates with tumor heterogeneity, stemness, and a suppressive immune microenvironment. In glioma, TSPAN4 enhances cell proliferation and promotes macrophage polarization toward the immunosuppressive M2 phenotype.ConclusionsTSPAN4, as a migrasome regulator, plays a crucial role in shaping the immunosuppressive tumor microenvironment in pan-cancer.
A novel monoclonal antibody against human thymic stromal lymphopoietin for the treatment of TSLP-mediated diseases
Authors: Shi Lihua , Yu Mingcan , Jin Ying , Chen Peng , Mu Guangmao , Tam Susan H. , Cho Minseon , Tornetta Mark , Han Chao , Fung Man-Cheong , Chiu Mark L. , Zhang Di 
Published: December 2024

IntroductionThymic stromal lymphopoietin (TSLP) is a master regulator of allergic inflammation against pathogens at barrier surfaces of the lung, skin, and gut. However, aberrant TSLP activity is implicated in various allergic, chronic inflammation and autoimmune diseases and cancers. Biologics drugs neutralizing excess TSLP activity represented by tezepelumab have been approved for severe asthma and are being evaluated for the treatments of other TSLP-mediated diseases.Methods and resultsIn this study, we discovered and characterized a novel humanized anti-TSLP antibody TAVO101 with high binding affinity to human TSLP, which blocks TSLP binding to its receptor complexes on cell surface. TAVO101 showed potent neutralization of TSLP activities in the TSLP-driven STAT5 reporter assay and cell proliferation assay. Results from ex vivo studies showed that TAVO101 neutralized TSLP-mediated CCL17 release from primary human CD1c+ dendritic cells and proliferation of activated CD4+ T cells. In addition, TAVO101 showed strong efficacy in both TSLP/OVA-induced asthma and imiquimod induced psoriasis models in hTSLP/hTSLPR double knock-in mice. We further conducted Fc engineering to optimize TAVO101 antibody with reduced affinity to Fcγ receptors and C1q protein but with increased affinity to FcRn receptor for half-life extension.DiscussionBy recognizing a different epitope, similarly potent neutralization of TSLP activities, and longer circulating half-life than tezepelumab, novel anti-TSLP antibody TAVO101 offers a potential best-in class therapeutics for various TSLP-mediated diseases.
SOX13 as a potential prognostic biomarker linked to immune infiltration and ferroptosis inhibits the proliferation, migration, and metastasis of thyroid cancer cells
Authors: Ma Yan-yan , Zhou Wei-ye , Qian Yue , Mu Ying-ying , Zhang Wei 
Published: December 2024

BackgroundSOX13 is a transcription factor belonging to the SOX family. SOX proteins are critical regulators of multiple cancer progression, and some are known to control carcinogenesis. Nevertheless, the functional and clinical significance of SOX13 in human thyroid cancer (THCA) remain largely unelucidated.MethodsData on SOX13 expression were obtained through The Cancer Genome Atlas together with Gene Expression Omnibus. Co-expression, differential expression, and functional analyses of genes were investigated by databases. Associations between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint gene levels were analyzed. Genetic changes in SOX13 were investigated using CBioPortal. Associations between SOX13 levels and THCA clinicopathological features were analyzed and nomogram modeling for diagnostic and prognostic prediction. The influence of SOX13 on proliferation, migration, and metastasis was determined in KTC-1 and TPC-1 cell lines.ResultsSOX13 was significantly lower in THCA tumors compared to controls. In addition, upregulated SOX13 gene mutation were evident in thyroid cancer. SOX13-associated genes exhibited differential expression in pathways associated with thyroid cancer development. Significant associations were found between SOX13 levels, immune infiltration, ferroptosis, and immune checkpoint genes in THCA tissue. SOX13 levels correlated with THCA stage, histologic grade, and primary neoplasm focus types, and independently predicted overall and progression-free intervals. SOX13 expression effectively distinguished between tumor and normal thyroid tissue. Spearman correlations highlighted a significant relationship between SOX13 and ferroptosis-associated genes. Overexpression of SOX13 enhances the inhibition of RSL3 (iron death activator) on the cell viability of TPC-1. Higher SOX13 levels in Thyroid cancer cells may lead to reduced proliferation, migration, and metastasis by regulating ferroptosis.ConclusionReduced SOX13 expression inversely impacts patient prognosis. In addition, SOX13 strongly regulates cancer immunity and Ferroptosis. Hence, SOX13 has great promise as a bioindicator for both thyroid cancer prognosis and immune cell invasion.
Identification of key genes related to growth of largemouth bass (Micropterus salmoides) based on comprehensive transcriptome analysis
Authors: Hu Dayan , Jian Jieliang , Zhang Jinpeng , Xu Xiaojun , Wang Shu , Gong Cuiping , Zhang Yuanqin , Zhu Pengcan , Gu Zhimin , Guan Wenzhi 
Published: December 2024

IntroductionLargemouth bass is an economically important farmed freshwater fish species that has delicious meat, no intermuscular thorns, and rapid growth rates. However, the molecular regulatory mechanisms underlying the different growth and developmental stages of this fish have not been reported.MethodsIn this study, we performed histological and transcriptomic analyses on the brain and dorsal muscles of largemouth bass at different growth periods. The brain and muscle tissue were dehydrated, embedded, sliced and stained with hematoxylin-eosin. Images were captured under a microscope and acquired using a microphotographic system. Differential expression between groups was analyzed using DESeq2. GO functional analysis and KEGG pathway analysis were then performed for differentially expressed genes. RT-qPCR validates the reliability of transcriptome sequencing data.ResultSmaller fish had more new muscle fiber numbers and wider intermuscular spaces compared to big specimens. Axons and nerve fibers were more pronounced in the telencephalons of big fish than in small fish. A total of 19,225 differentially expressed genes (DEGs) were detected in the muscle tissue, among which 7,724 were upregulated and 11,501 were downregulated, while a total of 5,373 DEGs were detected in the brain, among which 2,923 were upregulated and 2,450 were downregulated. GO and KEGG enrichment analyses indicated that nucleic acid binding, cytoskeletal motor activity, DNA binding, circadian rhythm, glycolysis/gluconeogenesis, and osteoclast differentiation were related to brain development while binding, cytoskeletal protein binding, biological processes, c-type lectin receptors, mitogen-activated protein kinase (MAPK) signaling pathways, and osteoclast differentiation were related to muscle growth. Stat3, pparg, akt1, mapk3, and mapk1 genes were mainly involved in the growth and development of largemouth bass.ConclusionThese results provide novel perspectives for deepening our understanding of the mechanisms underlying the growth and development and performing genetic selection in largemouth bass.
Identification of biomarkers and immune microenvironment associated with pterygium through bioinformatics and machine learning
Authors: Zhang Li-Wei , Yang Ji , Jiang Hua-Wei , Yang Xiu-Qiang , Chen Ya-Nan , Ying Wei-Dang , Deng Ying-Liang , Zhang Min-hui , Liu Hai , Zhang Hong-Lei 
Published: December 2024

BackgroundPterygium is a complex ocular surface disease characterized by the abnormal proliferation and growth of conjunctival and fibrovascular tissues at the corneal-scleral margin. Understanding the underlying molecular mechanisms of pterygium is crucial for developing effective diagnostic and therapeutic strategies.MethodsTo elucidate the molecular mechanisms of pterygium, we conducted a differential gene expression analysis between pterygium and normal conjunctival tissues using high-throughput RNA sequencing. We identified differentially expressed genes (DEGs) with statistical significance (adjust p &lt; 0.05, |logFC| &gt; 1). Enrichment analyses were performed to assess the biological processes and signaling pathways associated with these DEGs. Additionally, we utilized weighted correlation network analysis (WGCNA) to select module genes and applied Random Forest (RF) and Support Vector Machine (SVM) algorithms to identify pivotal feature genes influencing pterygium progression. The diagnostic potential of these genes was validated using external datasets (GSE2513 and GSE51995). Immune cell infiltration analysis was conducted using CIBERSORT to compare immune cell populations between pterygium and normal conjunctival tissues. Quantitative PCR (qPCR) was used to confirm the expression levels of the identified feature genes. Furthermore, we identified key miRNAs and candidate drugs targeting these feature genes.ResultsA total of 718 DEGs were identified in pterygium tissues compared to normal conjunctival tissues, with 254 genes showing upregulated expression and 464 genes exhibiting downregulated expression. Enrichment analyses revealed that these DEGs were significantly associated with inflammatory processes and key signaling pathways, notably leukocyte migration and IL-17 signaling. Using WGCNA, RF, and SVM, we identified KRT10 and NGEF as pivotal feature genes influencing pterygium progression. The diagnostic potential of these genes was validated using external datasets. Immune cell infiltration analysis demonstrated significant differences in immune cell populations between pterygium and normal conjunctival tissues, with an increased presence of M1 macrophages and resting dendritic cells in pterygium samples. qPCR analysis confirmed the elevated expression of KRT10 and NGEF in pterygium tissues.ConclusionOur findings emphasize the importance of gene expression profiling in unraveling the pathogenesis of pterygium. The identification of pivotal feature gene KRT10 and NGEF provide valuable insights into the molecular mechanisms underlying pterygium progression.
Impact of SARS-CoV-2 infection on patients with myasthenia gravis: a retrospective study in a Chinese population
Authors: Liu Peng , Li Mengna , Li Liqing , Jia Wenli , Dong Huimin , Qi Guoyan 
Published: December 2024

Background and purposeMyasthenia gravis (MG) is characterized by fluctuating muscle weakness due to immune-mediated damage to acetylcholine receptors. Viral infections can exacerbate symptoms of muscle weakness, and the clinical status of patients with MG may influence the outcomes of such infections. Here, we identified factors of symptom exacerbation, severe SARS-CoV-2 infection, and pneumonia in patients with MG who are infected with SARS-CoV-2.MethodsThe clinical characteristics and outcomes of 341 MG patients infected with SARS-CoV-2 across multiple regions in China were determined.ResultsThe median age of the patients was 49 years (range: 35–60 years) and the median disease duration was 4 years (range: 2–8 years). Among the patients, 67 (49.0%) were male and 174 (51.0%) were female. Multivariate analysis indicated that thymectomy [OR, 1.654 (95% CI, 1.036–2.643); p = 0.035], severe SARS-CoV-2 infection [OR, 4.275 (95% CI, 2.206–8.286); p &lt; 0.001], and pyridostigmine bromide [OR, 1.955 (95% CI, 1.192–3.206); p = 0.008] were associated with exacerbation of MG symptoms in patients infected with SARS-CoV-2. Age was significantly associated with severe SARS-CoV-2 infection [OR, 1.023 (95% CI, 1.001–1.046); p = 0.008], while patients with cardiac/vascular comorbidities exhibited an increased likelihood of severe SARS-CoV-2 infection [OR, 3.276 (95% CI, 1.027–10.449); p = 0.045]. Likewise, steroid treatment [OR, 6.140 (95% CI, 2.335–16.140); p &lt; 0.001] was associated with a significantly increased likelihood of severe SARS-CoV-2 infection compared with symptomatic treatment. Additionally, gender [OR, 0.323 (95% CI, 0.120–0.868); p = 0.025] and SARS-CoV-2 severity [OR, 6.067 (95% CI, 1.953–18.850); p = 0.002] were associated with the occurrence of pneumonia.ConclusionWe identified factors that were associated with the exacerbation of MG symptoms in patients infected with SARS-CoV-2, including thymectomy, severe SARS-CoV-2 infection, and the use of pyridostigmine bromide. Due to the retrospective nature of the study, these findings should be interpreted as associations rather than predictive factors. However, the results confirm the established relationships between severe SARS-CoV-2 infection and age, cardiovascular comorbidities, and the use of steroid treatment, suggesting that these factors should be considered when managing MG patients during SARS-CoV-2 infection.
The number of involved regions by prostate adenocarcinoma predicts histopathology concordance between radical prostatectomy specimens and MRI/ultrasound-fusion targeted prostate biopsy
Authors: Yusim Igor , Mazor Elad , Frumkin Einat , Hefer Ben , Li Sveta , Novack Victor , Mabjeesh Nicola J. 
Published: December 2024

IntroductionThe prostate biopsy (PB) results should be concordant with prostatectomy histopathology to avoid overestimating or underestimating the disease, leading to inappropriate or undertreatment of prostate cancer (PCa) patients. Since the introduction of multiparametric Magnetic Resonance Imaging (mpMRI) in the diagnostic pathway of PCa, most studies have shown that MRI/Ultrasound fusion-guided (MRI-fusion) PB improves concordance with histopathology of radical prostatectomy specimens. This study aimed to evaluate the improvement in concordance of prostatectomy specimens with PB histopathology obtained using the MRI-fusion approach compared with the 12-core TRUS-Bx and to identify the variables influencing this.Patients and methodsThe study included 218 men who were diagnosed with PCa by PB and underwent radical prostatectomy between 2016 and 2023. The patients were grouped based on the biopsy method: 115 underwent TRUS-Bx, and 103 underwent MRI-fusion PB. The histopathological grading of these biopsy approaches was compared with that of radical prostatectomy specimens. Multivariate logistic regression analyses were conducted to evaluate the impact of various criteria on histopathological concordance.ResultsIn patients with unfavorable intermediate- and high-risk PCa, MRI-fusion PB showed significantly better concordance with prostatectomy histopathology than TRUS-Bx (73.1% vs. 42.9%, p = 0.018). MRI-fusion PB had a significantly lower downgrading of prostatectomy histopathology than TRUS-Bx in all grade categories. The number of cancer-involved regions of the prostate is an independent predictor for concordance (OR = 1.24, 95%CI = 1.04-1.52, p = 0.02) and downgrading (OR = 0.46, 95%CI = 0.24-0.83, p = 0.01).ConclusionsUsing an MRI-fusion PB improves histopathological concordance in patients with unfavorable intermediate and high-risk PCa. It reduces the downgrading rate of prostatectomy histopathology compared with TRUS-Bx in all grade categories. The number of cancer-involved regions is an independent predictor of the concordance between biopsy and final histopathology after prostatectomy and post-prostatectomy histopathology downgrading. Our findings could assist in selecting PCa patients for AS and focal treatment based on the histopathology obtained from the MRI-fusion PB.
Executive functioning challenges of adolescents born extremely and very preterm
Authors: Lee Samantha J. , Woodward Lianne J. , Moor Stephanie , Austin Nicola C. 
Published: December 2024

BackgroundChildren born very preterm (VPT; &lt;32 weeks) are at increased risk of executive functioning (EF) difficulties. But less is known about the nature and extent of these executive difficulties during late adolescence, particularly across multiple EF domains and in response to varying degrees of executive demand.MethodsUsing data from a prospective longitudinal study, this paper describes the EF profiles of 92 VPT and 68 full-term (FT) adolescents at age 17 years. Relations between gestational age (GA) and later EF performance, in addition to neonatal predictors, were examined.ResultsVPT-born adolescents performed less well than FT adolescents across the domains of working memory, planning, and cognitive flexibility, with the largest differences observed for those born &lt;28 weeks GA (effect sizes −0.6 to −1.0 SD), and when task demands were high. The effects of GA on EF outcome were fully mediated by neonatal medical complexity (b = 0.169, t = −1.73) and term equivalent white matter abnormalities (b = 0.107, t = −3.33).ConclusionFindings support the need for long-term cognitive support for individuals born very preterm, particularly those exposed to high levels of medical and neurological risk, with these factors largely explaining associations between GA and EF outcome.
Latent class analysis for health-related quality of life in nurses in China
Authors: Zhao Yan , Yang Bei , Chu Jianying 
Published: December 2024

BackgroundThis study aimed to identify the types of quality of life (QoL) based on the five dimensions of the EQ-5D and predict factors affecting QoL.MethodsA multistage stratified cluster sampling survey was conducted among the staff of 12 general hospitals, 1,965 nurses completed the survey, and the data were analyzed using SPSS 26.0 and Mplus 8.3 for latent analysis.ResultsThree latent classes of QoL were identified: low-level (2.8%), pain and discomfort (7.6%), medium-level (47.1%), and high-level (42.5%). The types and characteristics of QoL differed among these latent classes. The low-level group had the lowest EQ visual analog scale (EQ-VAS) score (F = 75.217, P &lt; 0.001) and the highest K10 score (F = 61.90, P &lt; 0.001). Moreover, increased age (OR = 0.819, 95% CI: 0.817–0.973), never having drunk alcohol (OR = 0.107, 95% CI: 0.023, 0.488), and increased EQ-VAS scores (OR = 0.935, 95% CI: 0.919, 0.952) were protective factors for quality of life, while working in obstetrics and gynecology (OR = 6.457, 95% CI:1.852, 22.512) and higher K10 scores (OR = 1.153, 95% CI: 1.100, 1.209) were risk factors for quality of life.ConclusionThe results indicated significant heterogeneity in the types of QoL and identified predictors of QoL. These findings provide basic information for the development of nursing interventions to improve quality of life and identified specific characteristics that should be considered during intervention development.
Multidimensional screen exposure and its impact on psychological well-being in toddlers
Authors: Luo Sha , Guo Wenjie , Chen Hao , Zhu Yidong , Zhu Guowei , Jia Yingnan 
Published: December 2024

ObjectivePrevious studies have indicated a link between screen exposure and children’s mental health, but with the emergence of new screen media and a rise in screen content, uncertainties have grown. Our aim was to investigate the impact of screen use on psychological issues in 2- to 3-year-old children, considering screen time and types of screen media and content.MethodsThis cross-sectional study included participants from Shanghai, China, from February to July 2023. Screen use information was collected from children’s caregivers via online questionnaire. Psychological difficulties of children were reported by parents using the Strengths and Difficulties Questionnaire (SDQ).ResultsAmong the interviewed children, 15.9% had an average daily screen time exceeding 1 hour (h). 52.1% of them viewed inappropriate, non-child-directed screen content, 37.6% were mainly exposed to educational content, and 18.9% watched more fast-paced screen content than slow-paced content. Multivariate regression analysis revealed that the use of mobile phones (β = 1.16, 95% CI: 0.14, 2.18), virtual reality (VR) devices (β = 2.57, 95% CI: 0.62, 4.53) and computers for more than 30 minutes (min) per day (β = 2.15, 95% CI: 0.99, 3.30) were related to higher SDQ difficulty scores. Watching more fast-paced (β = 1.58, 95% CI: 0.80, 2.35) and more noneducational screen content (β = 1.01, 95% CI: 0.35, 1.66) were also associated with increased difficulty scores.ConclusionThe amount of time spent using computers, mobile phones and VR devices and the proportion of exposure to noneducational content and fast-paced content were significantly associated with psychological problems among 2- to 3-year-old children.