bluuebunny/crossref_metadata_2025 huggingface dataset:
MODEL DISCOVERY LEARNING UNTUK MENINGKATKAN HASIL BELAJAR SISWA KELAS VII SMP
Authors: Novi Novi Hefriyanti , Juanda
Published: August 2024

This research aims to increase student understanding, increase student creativity and activeness, and improve the quality of student learning outcomes regarding procedural texts through discovery learning models. The learning model applied by the teacher will affect student understanding. Low student understanding will affect student learning outcomes related to procedure text material. The source of this research data is information obtained from Class VII Junior High School students using random sampling of 20 students. The time of the study was conducted in November 2022. The data collected are quantitative data and qualitative data. Quantitative data is obtained from formative test results, and student learning outcomes. Data collection techniques use observation, documentation, and interviews. The results showed that there was an increase in student learning outcomes after learning with the discovery learning model, there were significant differences related to student learning outcomes in cycle I and cycle II. The result of the first cycle is that from the number of students as many as 20, there are 12 (60%) students who get scores above 70, and 8 (40%) students get scores below 70 with an average score of 72.05. In the second cycle, all 20 students scored above 70 with an average score of 76.35.
A robust multimodal detection system: physical exercise monitoring in long-term care environments
Authors: Al Mudawi Naif , Batool Mouazma , Alazeb Abdulwahab , Alqahtani Yahay , Almujally Nouf Abdullah , Algarni Asaad , Jalal Ahmad , Liu Hui
Published: August 2024

Introduction

Falls are a major cause of accidents that can lead to serious injuries, especially among geriatric populations worldwide. Ensuring constant supervision in hospitals or smart environments while maintaining comfort and privacy is practically impossible. Therefore, fall detection has become a significant area of research, particularly with the use of multimodal sensors. The lack of efficient techniques for automatic fall detection hampers the creation of effective preventative tools capable of identifying falls during physical exercise in long-term care environments. The primary goal of this article is to examine the benefits of using multimodal sensors to enhance the precision of fall detection systems.

Methods

The proposed paper combines time–frequency features of inertial sensors with skeleton-based modeling of depth sensors to extract features. These multimodal sensors are then integrated using a fusion technique. Optimization and a modified K-Ary classifier are subsequently applied to the resultant fused data.

Results

The suggested model achieved an accuracy of 97.97% on the UP-Fall Detection dataset and 97.89% on the UR-Fall Detection dataset.

Discussion

This indicates that the proposed model outperforms state-of-the-art classification results. Additionally, the proposed model can be utilized as an IoT-based solution, effectively promoting the development of tools to prevent fall-related injuries.
A quest for stakeholder synchronization in the CAR T-cell therapy supply chain
Authors: Holland Shelby M. , Sohal Amrik , Nand Alka Ashwini , Hutmacher Dietmar W.
Published: August 2024

Advancements in cell therapy have the potential to improve healthcare accessibility for eligible patients. However, there are still challenges in scaling production and reducing costs. These challenges involve various stakeholders such as the manufacturing facility, third-party logistics (3PL) company, and medical center. Proposed solutions tend to focus on individual companies rather than addressing the interconnectedness of the supply chain’s challenges. The challenges can be categorized as barriers from product characteristics, regulatory requirements, or lagging infrastructure. Each barrier affects multiple stakeholders, especially during a boundary event like product handover. Therefore, solutions that only consider the objectives of one stakeholder fail to address underlying problems. This review examines the interconnecting cell therapy supply chain challenges and how they affect the multiple stakeholders involved. The authors consider whether proposed solutions impact individual stakeholders or the entire supply chain and discuss the benefits of stakeholder coordination-focused solutions such as integrated technologies and information tracking. The review highlights how coordination efforts allow for the implementation of widely-supported cell therapy supply solutions such as decentralized manufacturing through stakeholder collaboration.
CRISPR-Cas9 screening develops an epigenetic and transcriptional gene signature for risk stratification and target prediction in neuroblastoma
Authors: Zhang Liaoran , Mo Jialin , Shi Hao , Xiong Jing , Aierken Yeerfan , Chen Feng , Tang Yujie , Zhao Kewen , Lv Zhibao , Tan Kezhe
Published: August 2024

Objectives: Neuroblastoma (NB), a pediatric malignancy of the peripheral nervous system, is characterized by epigenetic and transcriptional (EP-TF) anomalies. This study aimed to develop an EP-TF clinical prognostic model for NB using CRISPR-Cas9 knockout screening.

Results: An integrative analysis was conducted using CRISPR-Cas9 screening in vitro and in vivo with public NB datasets to identify 35 EP-TF genes that exhibited the highest expression in NB and were highly dependent on cancer viability. After univariate analysis, 27 of these 35 genes were included in the least absolute shrinkage and selection operator screen. We established and biologically validated a prognostic EP-TF model encompassing RUVBL1, LARP7, GTF3C4, THAP10, SUPT16H, TIGD1, SUV39H2, TAF1A, SMAD9, and FEM1B across diverse NB cohorts. MYCN serves a potential upstream regulator of EP-TF genes. The high-risk subtype exhibited traits associated with the malignant cell cycle, MYCN-linked signaling and chromatin remodeling, all of which are correlated with poor prognosis and immunosuppression. MEK inhibitors have emerged as promising therapeutic agents for targeting most EP-TF risk genes in NB.

Conclusion: Our novel prognostic model shows significant potential for predicting and evaluating the overall survival of NB patients, offering insights into therapeutic targets.
Gut microbiota, circulating inflammatory proteins and sepsis: a bi-directional Mendelian randomization study
Authors: Li Zuming , Lin Liangcai , Kong Yunqi , Feng Jieni , Ren Xiaolei , Wang Yushi , Chen Xueru , Wu Siyi , Yang Rongyuan , Li Jiqiang , Liu Yuntao , Lu Yue , Chen Jiankun
Published: August 2024

Background

Gut microbiota is closely related to the occurrence and development of sepsis. However, the causal effects between the gut microbiota and sepsis, and whether circulating inflammatory proteins act as mediators, remain unclear.

Methods

Gut microbiota, circulating inflammatory proteins, and four sepsis-related outcomes were identified from large-scale genome wide association studies (GWAS) summary data. Inverse Variance Weighted (IVW) was the primary statistical method. Additionally, we investigated whether circulating inflammatory proteins play a mediating role in the pathway from gut microbiota to the four sepsis-related outcomes.

Results

There were 14 positive and 15 negative causal effects between genetic liability in the gut microbiota and four sepsis-related outcomes. Additionally, eight positive and four negative causal effects were observed between circulating inflammatory proteins and the four sepsis-related outcomes. Circulating inflammatory proteins do not act as mediators.

Conclusions

Gut microbiota and circulating inflammatory proteins were causally associated with the four sepsis-related outcomes. However, circulating inflammatory proteins did not appear to mediate the pathway from gut microbiota to the four sepsis-related outcomes.
A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study
Authors: Zhong Wenting , Yan Lanzhi , Zhu Yage , Shi Lei , He Yingli , Chen Tianyan , Zheng Jie
Published: August 2024

Background and aims

Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure.

Methods

A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks.

Results

At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported.

Conclusion

Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.
Case Report: Epi-endocardial bridges in refractory cavotricuspid isthmus-dependent atrial flutter: technical analysis of epi-endocardial breakthrough
Authors: Matteucci Andrea , Pandozi Claudio , Russo Maurizio , Galeazzi Marco , Lombardi Enrico , Mariani Marco Valerio , Lavalle Carlo , Colivicchi Furio
Published: August 2024

Background

Typical isthmus-dependent atrial flutter (AFL) is traditionally treated through radiofrequency (RF) ablation to create a bidirectional conduction block across the cavo-tricuspid isthmus (CTI) in the right atrium. While this approach is successful in many cases, certain anatomical variations can present challenges, making CTI ablation difficult.

Methods

We enrolled four patients with typical counter-clockwise AFL who displayed an epicardial bridge at the CTI. Patients underwent high-resolution mapping of the right atrium and CTI ablation.

Results

Post-mapping identified areas of early focal activation outside the lesion line which suggested the presence of an epi-endocardial bridge with an endocardial breakthrough, confirmed by recording a unipolar rS pattern on electrograms at that site. A stable CTI block was achieved in all patients only after ablation at the site of the epi-endocardial breakthrough.

Conclusions

The presence of an epicardial bridge at the CTI, allowing conduction to persist despite endocardial ablation, should be considered in challenging cases of CTI-dependent AFL. Understanding this phenomenon and utilizing appropriate mapping and ablation techniques are essential for achieving successful and lasting CTI block.
Analyzing the barriers and enablers to internet hospital implementation: a qualitative study of a tertiary hospital using TDF and COM-B framework
Authors: Wu Xiaolong , Kuang Yulin , Guo Yonglin , Wei Ning , Fan Zichun , Ling Jingru
Published: August 2024

Background

Internet hospitals have become an important way to improve the accessibility of medical services and promote medical equity in China. However, there is still lack of research on the behavior of medical personnel during the process of using Internet medical services, and the elements of behavior that motivate doctors to actively use or resist the use of Internet hospitals are still not fully analyzed. The study applied the Theoretical Domains Framework to examine the factors affecting the engagement of medical personnel in Internet hospitals, with the aim of guiding the design of intervention to enhance Internet hospital participation.

Methods

This study utilized qualitative analysis. Semi-structured questionnaires based on the Theoretical Domains Framework (TDF) and Capability-Opportunity-Motivation-Behavior (COM-B) model was developed and administered to 40 doctors and nurses at a Grade A tertiary hospital in Guangdong Province. Data was coded and analyzed using qualitative methods including Nvivo software.

Results

The research displayed 19 barriers and 7 enablers for the implementation of Internet hospitals, all 14 TDF domains impacted participation with motivation cited most frequently. Despite challenges, medical personnel exhibited a generally optimistic stance towards utilization of the Internet hospital. Major barriers include the higher requirement of diagnostic ability, objective difficulties brought by online consultation to the decision-making process, limitation of time and other resources, not ideal technological and institutional environment, lack of self-efficacy and negative expectation of results in online consultation. Key enablers include patient needs and the positive impact of online care on the medical process and patient experience.

Discussion

This qualitative study identified a range of barriers and enablers to Internet hospital participation according to medical personnel, providing an conceptual framework to guide further research evaluating implementation strategies. Expanded research and targeted interventions design can help optimize participation in this evolving healthcare delivery model.
Learning lexical tone through statistical learning in non-tone language speakers
Authors: Tang Mi , Spenader Jennifer , Jones Stephen
Published: August 2024

This study investigates the role of statistical learning in the learning of lexical tones by non-tone language speakers. Over two experiments, participants were exposed to tone-syllable combinations with conditioned patterns. Experiment 1 used a typical statistical learning paradigm without feedback to assess participants' ability to discriminate tone-syllable combinations. The results revealed significant syllable learning but not tone learning. Experiment 2 controlled for syllable occurrence to isolate the learning of tonal patterns and demonstrated above-chance learning accuracy from the first training day, indicating successful lexical tone learning through the statistical learning mechanisms. The findings suggest that statistical learning without feedback facilitates lexical tone learning. Our study not only supports the universality of statistical learning in language acquisition but also prompts further research into its application in educational settings for teaching tonal languages.
Crafting personalized learning paths with AI for lifelong learning: a systematic literature review
Authors: Bayly-Castaneda K. , Ramirez-Montoya M-S. , Morita-Alexander A.
Published: August 2024

The rapid evolution of knowledge requires constantly acquiring and updating skills, making lifelong learning crucial. Despite decades of artificial intelligence, recent advances promote new solutions to personalize learning in this context. The purpose of this article is to explore the current state of research on the development of artificial intelligence-mediated solutions for the design of personalized learning paths. To achieve this, a systematic literature review (SRL) of 78 articles published between 2019 and 2024 from the Scopus and Web or Science databases was conducted, answering seven questions grouped into three themes: characteristics of the published research, context of the research, and type of solution analyzed. This study identified that: (a) the greatest production of scientific research on the topic is developed in China, India and the United States, (b) the focus is mainly directed towards the educational context at the higher education level with areas of opportunity for application in the work context, and (c) the development of adaptive learning technologies predominates; however, there is a growing interest in the application of generative language models. This article contributes to the growing interest and literature related to personalized learning under artificial intelligence mediated solutions that will serve as a basis for academic institutions and organizations to design programs under this model.
Long-term efficacy of lobectomy for stage T1 papillary thyroid carcinoma with varying degrees of lymph node metastasis
Authors: Qin Chao , Cai Sijia , Qi Yanyu , Liu Meilin , Xu Weibo , Yin Min , Tang Haitao , Ji Qinghai , Liao Tian , Wang Yu
Published: August 2024

Background

The presence of lymph node metastasis (LNM) is frequently observed in papillary thyroid carcinoma (PTC), and most clinical guidelines recommend total thyroidectomy. However, the impact of LNM on specific types of locoregional recurrence remains uncertain, particularly for stage T1 PTC.

Methods

The present retrospective cohort study enrolled patients diagnosed with stage T1 PTC between 2008 and 2015. Propensity score matching was performed in patients with lobectomy accompanied by varying degrees of LNM. Logistic regression analysis was performed to compare the effect of LNM on relapse types, and Kaplan-Meier method was utilized to calculate recurrence-free survival.

Results

The study cohort comprised 2,785 patients who were followed up for an average duration of 69 months. After controlling follow-up time and potential prognostic factors, we include a total of 362 patients in each group. Recurrence rates in the N0, N1a, and N1b groups were found to be 2.5%, 9.7%, and 10.2% respectively. Notably, group N1a versus group N0 (P=0.803), N1b group versus N0 group (P=0.465), and group N1b versus group N1a (P=0.344) had no difference in residual thyroid recurrence. However, when considering lymph node recurrence, both N1a(P=0.003) and N1b(P=0.009) groups showed a higher risk than N0 group. In addition, there was no difference in lymph node recurrence between N1b group and N1a group (P=0.364), but positive lymph node (PLN) and lymph node positive rate (LNPR) demonstrated a strong discriminatory effect (P<0.001).

Conclusion

Lobectomy may be more appropriate for patients with unilateral stage T1 PTC in the low LNPR group.
Role of renewable energy and storage in low-carbon power systems
Authors: Wang Weiru , Cheng Xueting , Li Jing , Zheng Huiping , Li Mengzan
Published: August 2024

To promote the achievement of low-carbon goals in the power industry, rational and effective power system planning is essential. The participation of demand response in power system planning is an important means to reduce carbon emissions. To this end, a dual-layer low-carbon planning model for power systems considering carbon emission flow and demand response was designed. The upper layer investment planning model minimizes investment and operational costs, using an annual 8760-h operation simulation model and unit clustering linearization of the coal-fired units, coordinating the optimized investment and construction capacity of traditional units, new energy, and storage. The lower layer model forms a demand response model based on carbon emission flow theory and a load-side stepped carbon price mechanism, using the unit output and line flow data calculated by the upper layer model. This model reasonably adjusts the load distribution to reduce both the amount and cost of carbon emissions. Finally, the proposed model was analyzed and verified on the improved IEEERTS-24 node system.
Signal partitioning between native and introduced forest birds of Hawai‘i Island
Authors: Hunt Noah J. , Ibanez Thomas , Pack Adam A. , Hart Patrick J.
Published: August 2024

Birds use sound for conspecific communication. According to the acoustic niche hypothesis, they avoid signal competition with other species by partitioning sound in frequency and time. Others have observed introduced species changing the vocal behavior of native species; however, community-level effects of multiple introduced species remain unknown. Hawai‘i, with its legacy of bird extinctions followed by a surge of human introductions, offers a unique opportunity to study acoustic signal partitioning between native and introduced species. We predicted that communities with higher percentages of introduced birds would exhibit more acoustic overlap between members of different species due to shorter time frames to evolve signal partitioning. Using autonomous recording units, we recorded forest bird communities during the summer in montane primary and secondary forests as well as a low-elevation agricultural site. Random samples of recordings from each site were visualized as spectrograms, and all bird vocalizations ≥5 decibels above background noise were identified and labeled by species. Frequency range and the proportion of overlap with other species were compared between native and introduced species. We also used a null model which randomized the start time of each bird vocalization within a location over 500 iterations, then compared the amount of heterospecific signal overlap in the randomizations to that observed in the recordings. While native and introduced species generally used similar frequency ranges, native-native heterospecific species vocalization pairs had a significantly higher proportion of overlap than introduced-native and native-native pairs. Additionally, the incidence of signal overlap in the original recordings tended to be lower than in the null model randomizations, but this difference was not significant, and was not influenced by the percentage of introduced species vocalizations at the site. The lack of significant difference between observed and null model signal overlap occurrence suggests that native and introduced forest birds were not partitioning acoustic space either spectrally or temporally, and that introduced birds are not strongly influencing signal partitioning in forest bird communities of Hawai‘i. However, this may have been a consequence of recording during the non-breeding season, and future work should compare vocal activity in native and introduced birds throughout the year.
Unveiling potential drug targets for lung squamous cell carcinoma through the integration of druggable genome and genome-wide association data
Authors: Wu Wenhua , Chen Zhengrui , Wen Haiteng , Zhang Haiyun
Published: August 2024

Background: Lung squamous cell carcinoma (LSCC) is a major subtype of lung cancer with poor prognosis and low survival rate. Compared with lung adenocarcinoma, yet no FDA-approved targeted-therapy has been found for lung squamous cell carcinoma.

Methods: To identify potential drug targets for LSCC, Summary-data-based Mendelian randomization (SMR) analysis was used to examine the potential association between 4,543 druggable genes and LSCC, followed by colocalization analysis and HEIDI tests to confirm the robustness of the result. Phenome-wide association study (PheWAS) explored potential side effects of candidate drug targets. Enrichment analysis and protein-protein interaction networks revealed the function and significance of therapeutic targets. Single-cell expression analysis was used to examine cell types with enrichment expression of druggable genes in LSCC tissue. Drug prediction included screening potential drug candidates and evaluating their interactions with targets through molecular docking.

Results: This research has identified ten significant drug targets for LSCC through a comprehensive SMR analysis. These targets included (COPA, PKD2L1, CCR1, C2, CYP21A2, and NCSTN as risk factors, and CCNA2, C4A, APOM, and LPAR2 as protective factors). PheWAS demonstrated that C2, CCNA2, LPAR2, and NCSTN exhibited associations with other phenotypes at the genetic level. Then, we found four potentially effective drugs with the Dsigdb database. Subsequently, molecular docking indicated that favorable binding interactions between drug candidates and potential target molecules. In the druggability evaluation, five out of ten drug target genes have been used in drug development (APOM, C4A, CCNA2, COPA, and PKD2L1). Six out of ten druggable genes showed significant expression in LSCC tissues (COPA, PKD2L1, CCR1, C2, NCSTN, LPAR2). Besides, Single-cell expression analysis revealed that C2 and CCNA2 were primarily enriched in macrophages, while COPA and NCSTN were enriched in both macrophages and epithelial cells.

Conclusion: Our research revealed ten potential druggable genes for LSCC treatment, which might help to advance the precise and efficient therapeutic approaches of LSCC.
Unveiling the bioinformatic genes and their involved regulatory mechanisms in type 2 diabetes combined with osteoarthritis
Authors: Mao Guangming , Xu Wenhao , Wan Lingli , Wang Hongpin , Xu Shutao , Zhang Liangming , Li Shiyang , Zhang Jifa , Lai Zhongming , Lan Yuping , Liu Jianhui
Published: August 2024

Background

Type 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA.

Methods

T2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking.

Results

In this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA.

Conclusion

This study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition.
New-onset autoantibodies to selenoprotein P following severe burn injury
Authors: Turan Tabael L. , Klein Holger J. , Graf Theresia Reding , Chillon Thilo Samson , Plock Jan A. , Schomburg Lutz
Published: August 2024

The liver-derived selenium (Se) transporter selenoprotein P (SELENOP) declines in critical illness as a negative acute phase reactant and has recently been identified as an autoantigen. Hepatic selenoprotein biosynthesis and cotranslational selenocysteine insertion are sensitive to inflammation, therapeutic drugs, Se deficiency, and other modifiers. As severe burn injury induces a heavy inflammatory burden with concomitant Se depletion, we hypothesized an impairment of selenoprotein biosynthesis in the acute post-burn phase, potentially triggering the development of autoantibodies to SELENOP (SELENOP-aAb). To test this hypothesis, longitudinal serum samples from severely burned patients were analyzed over a period of six months. Newly occurring SELENOP-aAb were detected in 8.4% (7/83) of the burn patients, with onset not earlier than two weeks after injury. Prevalence of SELENOP-aAb was associated with injury severity, as aAb-positive patients have suffered more severe burns than their aAb-negative counterparts (median [IQR] ABSI: 11 [7–12] vs. 7 [5.8–8], p = 0.023). Autoimmunity to SELENOP was not associated with differences in total serum Se or SELENOP concentrations. A positive correlation of kidney-derived glutathione peroxidase (GPx3) with serum SELENOP was not present in the patients with SELENOP-aAb, who showed delayed normalization of GPx3 activity post-burn. Overall, the data suggest that SELENOP-aAb emerge after severe injury in a subset of patients and have antagonistic effects on Se transport. The nature of burn injury as a sudden event allowed a time-resolved analysis of a direct trigger for new-onset SELENOP-aAb, which may be relevant for severely affected patients requiring intensified acute and long-term care.
In silico evaluation of the role of Fab glycosylation in cetuximab antibody dynamics
Authors: Saporiti Simona , Bianchi Davide , Ben Mariem Omar , Rossi Mara , Guerrini Uliano , Eberini Ivano , Centola Fabio
Published: August 2024

Introduction

N-glycosylation is a post-translational modification that is highly important for the development of monoclonal antibodies (mAbs), as it regulates their biological activity, particularly in terms of immune effector functions. While typically added at the Fc level, approximately 15-25% of circulating antibodies exhibit glycosylation in the Fab domains as well. To the best of our knowledge, cetuximab (Erbitux®) is the only therapeutic antibody presenting Fab glycosylation approved world-wide targeting the epidermal growth factor receptor for the treatment of metastatic-colorectal and head and neck cancers. Additionally, it can trigger antibody-dependent cell cytotoxicity (ADCC), a response that typically is influenced by N-glycosylation at Fc level. However, the role of Fab glycosylation in cetuximab remains poorly understood. Hence, this study aims to investigate the structural role of Fab glycosylation on the conformational behavior of cetuximab.

Methods

The study was performed in silico via accelerated molecular dynamics simulations. The commercial cetuximab was compared to its form without Fab glycosylation and structural descriptors were evaluated to establish conformational differences.

Results

The results clearly show a correlation between the Fab glycosylation and structural descriptors that may modulate the conformational freedom of the antibody, potentially affecting Fc effector functions, and suggesting a negative role of Fab glycosylation on the interaction with FcγRIIIa.

Conclusion

Fab glycosylation of cetuximab is the most critical challenge for biosimilar development, but the differences highlighted in this work with respect to its aglycosylated form can improve the knowledge and represent also a great opportunity to develop novel strategies of biotherapeutics.
Multi-transcriptomics analysis of microvascular invasion-related malignant cells and development of a machine learning-based prognostic model in hepatocellular carcinoma
Authors: Huang Haoran , Wu Feifeng , Yu Yang , Xu Borui , Chen Dehua , Huo Yuwei , Li Shaoqiang
Published: August 2024

Background

Microvascular invasion (MVI) stands as a pivotal pathological hallmark of hepatocellular carcinoma (HCC), closely linked to unfavorable prognosis, early recurrence, and metastatic progression. However, the precise mechanistic underpinnings governing its onset and advancement remain elusive.

Methods

In this research, we downloaded bulk RNA-seq data from the TCGA and HCCDB repositories, single-cell RNA-seq data from the GEO database, and spatial transcriptomics data from the CNCB database. Leveraging the Scissor algorithm, we delineated prognosis-related cell subpopulations and discerned a distinct MVI-related malignant cell subtype. A comprehensive exploration of these malignant cell subpopulations was undertaken through pseudotime analysis and cell-cell communication scrutiny. Furthermore, we engineered a prognostic model grounded in MVI-related genes, employing 101 algorithm combinations integrated by 10 machine-learning algorithms on the TCGA training set. Rigorous evaluation ensued on internal testing sets and external validation sets, employing C-index, calibration curves, and decision curve analysis (DCA).

Results

Pseudotime analysis indicated that malignant cells, showing a positive correlation with MVI, were primarily concentrated in the early to middle stages of differentiation, correlating with an unfavorable prognosis. Importantly, these cells showed significant enrichment in the MYC pathway and were involved in extensive interactions with diverse cell types via the MIF signaling pathway. The association of malignant cells with the MVI phenotype was corroborated through validation in spatial transcriptomics data. The prognostic model we devised demonstrated exceptional sensitivity and specificity, surpassing the performance of most previously published models. Calibration curves and DCA underscored the clinical utility of this model.

Conclusions

Through integrated multi-transcriptomics analysis, we delineated MVI-related malignant cells and elucidated their biological functions. This study provided novel insights for managing HCC, with the constructed prognostic model offering valuable support for clinical decision-making.
Potentially functional variants of INPP5D and EXOSC3 in immunity B cell-related genes are associated with non-small cell lung cancer survival
Authors: Lu Guojun , Liu Hongliang , Wang Huilin , Tang Xiaozhun , Luo Sheng , Du Mulong , Christiani David C. , Wei Qingyi
Published: August 2024

B cells are adaptive immune cells in the tumor microenvironment and play an important role in tumor development and metastasis. However, the roles of genetic variants of the immunity B cell-related genes in the survival of patients with non-small cell lung cancer (NSCLC) remain unknown. In the present study, we first evaluated associations between 10,776 single nucleotide polymorphisms (SNPs) in 220 immunity B cell-related genes and survival of NSCLC in a discovery dataset of 1,185 patients from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We found that 369 SNPs were significantly associated with overall survival (OS) of NSCLC in multivariable Cox proportional hazards regression analysis (P ≤ 0.05, Bayesian false discovery probability ≤ 0.80), of which 18 SNPs were validated in another independent genotyping dataset of 984 patients from the Harvard Lung Cancer Susceptibility (HLCS) Study. We then performed linkage disequilibrium (LD) analysis, followed by stepwise analysis with a multivariable Cox regression model. Finally, two independent SNPs, inositol polyphosphate-5-phosphatase D (INPP5D) rs13385922 C>T and exosome component 3 (EXOSC3) rs3208406 A>G, remained significantly associated withNSCLC OS with a combined hazards ratio (HR) of 1.14 (95% confidence interval = 1.06-1.23, P = 2.41×10-4) and 1.20 (95% confidence interval = 1.14-1.28, P = 3.41×10-9), respectively. Furthermore, NSCLC patients with the combination of unfavorable genotypes for these two SNPs were associated with a poor OS (Ptrend = 0.0002) and disease-specific survival (DSS, Ptrend < 0.0001) in the PLCO dataset. Expression quantitative trait loci (eQTL) analysis suggested that the INPP5D rs6782875 T allele was significantly correlated with elevated INPP5D mRNA expression levels in normal lung tissues and whole blood samples, while the EXOSC3 rs3208406 G allele was significantly correlated with increased EXOSC3 mRNA expression levels in normal lung tissues. Our data indicated that genetic variants in these immunity B cell-related genes may predict NSCLC survival possibly by influencing the gene expression.
Extracellular vesicles derived from antigen-presenting cells pulsed with foot and mouth virus vaccine-antigens act as carriers of viral proteins and stimulate B cell response
Authors: Menay Florencia , Cocozza Federico , Gravisaco Maria J. , Elisei Analia , Re Javier Ignacio , Ferella Alejandra , Waldner Claudia , Mongini Claudia
Published: August 2024

Foot and mouth disease (FMD) is a highly contagious infection caused by FMD-virus (FMDV) that affects livestock worldwide with significant economic impact. The main strategy for the control is vaccination with FMDV chemically inactivated with binary ethylenimine (FMDVi). In FMDV infection and vaccination, B cell response plays a major role by providing neutralizing/protective antibodies in animal models and natural hosts. Extracellular vesicles (EVs) and small EVs (sEVs) such as exosomes are important in cellular communication. EVs secreted by antigen-presenting cells (APC) like dendritic cells (DCs) participate in the activation of B and T cells through the presentation of native antigen membrane-associated to B cells or by transferring MHC-peptide complexes to T cells and even complete antigens from DCs. In this study, we demonstrate for the first time that APC activated with the FMDVi O1 Campos vaccine-antigens secrete EVs expressing viral proteins/peptides that could stimulate FMDV-specific immune response. The secretion of EVs-FMDVi is a time-dependent process and can only be isolated within the first 24 h post-activation. These vesicles express classical EVs markers (CD9, CD81, and CD63), along with immunoregulatory molecules (MHC-II and CD86). With an average size of 155 nm, they belong to the category of EVs. Studies conducted in vitro have demonstrated that EVs-FMDVi express antigens that can stimulate a specific B cell response against FMDV, including both marginal zone B cells (MZB) and follicular B cells (FoB). These vesicles can also indirectly or directly affect T cells, indicating that they express both B and T epitopes. Additionally, lymphocyte expansion induced by EVs-FMDVi is greater in splenocytes that have previously encountered viral antigens in vivo. The present study sheds light on the role of EVs derived from APC in regulating the adaptive immunity against FMDV. This novel insight contributes to our current understanding of the immune mechanisms triggered by APC during the antiviral immune response. Furthermore, these findings may have practical implications for the development of new vaccine platforms, providing a rational basis for the design of more effective vaccines against FMDV and other viral diseases.
The associations between common neuroimaging parameters of Progressive Supranuclear Palsy in magnetic resonance imaging and non-specific inflammatory factors – pilot study
Authors: Alster Piotr , Otto-Ślusarczyk Dagmara , Kutyłowski Michał , Migda Bartosz , Wiercińska-Drapało Alicja , Jabłońska Joanna , Struga Marta , Madetko-Alster Natalia
Published: August 2024

Progressive Supranuclear Palsy is an atypical parkinsonism based on tauopathic pathology. Growing interest is associated with the pathomechanism of this disease. Among theories analyzing this issue can be mentioned the one highlighting the significance of inflammation. In this study authors examined 14 patients with PSP-Richardson syndrome (PSP-RS) and 13 healthy volunteers using laboratory testing based on the analysis of interleukins 1 and 6 (IL-1 and IL-6), tau in the cerebrospinal fluid (CSF) and non-specific parameters of peripheral inflammation in the serum (IL-1, IL-6, neutrophils, lymphocytes, monocytes, platelets and the ratios based on the factors). All of the patients underwent neuroimaging using magnetic resonance imaging using 3 Tesla. The serum levels of IL-1 were positively correlated with the area of the mesencephalon, suggesting that higher levels of IL-1 are not linked with atrophic changes in this region, whereas serum levels IL-6 was positively correlated with frontal horn width and negatively correlated with superior cerebellar area. Additionally IL-6 in the serum was found to be correlated with neutrophil-to-high density lipoprotein ratio. The observations were not confirmed in the analysis of the levels of interleukins in the CSF. To the best of our knowledge this work is one of the first analyzing this issue. The outcome of the work shows that the role of interleukins associated with microglial activation may possibly differ in the context of neurodegenerative changes, moreover the role of peripheral inflammation in PSP requires further analysis.
Sustaining success through strategies for post-elimination management of neglected tropical diseases in African Union Member States
Authors: Chotun Nafiisah , Eaton Julian , Anagbogu Ifeoma Ajegbo , Tesfahunei Hanna Amanuel , Shawa Sheila , Karutu Carol , Bolarinwa Akeem , Mohammed Abdulaziz
Published: August 2024

The elimination of Neglected Tropical Diseases (NTDs) has seen significant progress, with 22 African Union Member States having successfully eliminated at least one NTD. However, post-elimination management of NTDs remains a challenge. This article provides important insights into the challenges faced by African Union Member States after eliminating NTDs, including potential financial support withdrawal and risk of disease reemergence. We also discuss comprehensive strategies for post-elimination management, emphasising the importance of robust surveillance systems, capacity building, community engagement, and the integration of mental health services. We also advocate for a multisectoral approach to sustain elimination gains, aligning with global and regional health strategies. Our analysis underscores the necessity of continuous innovation in surveillance, the critical role of community health workers, the integration of NTD post-elimination management into broader health and development frameworks such as Universal Healthcare Coverage, and the need for innovative financing and partnerships to ensure the long-term success of NTD elimination efforts.
Molecular characterization of fad6 gene and its transcriptional changes in response to different initial diets and nutritional status in yellow catfish (Pelteobagrus fulvidraco)
Authors: Zhou Bo , Wei Xiu-Ying , Wen Zheng-Yong , Wang Bin , Zhao Yu-Ying , Zeng Wan-Hong , He Yu , Prathomya Panita , Lv Yun-Yun , Li Yan-Ping , Wang Jun , Li Rui , Li Xu-Guang , Zhou Jun , Zhang Shi-Yong , Fan Jun-De , Shi Qiong
Published: August 2024

Fatty acid desaturases (FADs) are rate-limiting enzymes for the biosynthesis of highly unsaturated fatty acids (HUFAs). As a new member of the FAD family, Fad6 and its roles remain unclear in various teleost fishes. In this study, we identified a fad6 gene from yellow catfish (ycfad6) and determined its spatiotemporal expression patterns and responses to different initial diets and nutritional status in yellow catfish. Our results showed that the open reading frame (ORF) of ycfad6 was 1,080 bp in length, encoding a protein of 359 amino acids. Multiple protein sequences alignment proved that fad6 is highly conserved among diverse vertebrates. Meanwhile, phylogenetic analysis revealed that Southern catfish and yellow catfish were clustered into one branch, supporting evolutionary consistence between the fad6 gene and fish morphology. Moreover, comparisons of genomic synteny and gene structure revealed functional and evolutionary conservation of the fad6 gene in various teleost fishes. Tissue distribution analysis by quantitative RT-PCR demonstrated that the ycfad6 gene was extensively expressed in examined tissues, with higher transcription levels in the heart and liver. Meanwhile, ycfad6 gene was widely expressed in various developmental stages, indicating Fad6 may play important roles in HUFA biosynthesis at early developmental stages in yellow catfish. Functional experiments verified that the transcription of ycfad6 decreased significantly with the extension of feeding time (with egg yolk or Artemia nauplii) at the early developmental stages, indicating that a diet rich in HUFA can remarkably inhibit the transcription of ycfad6 in yellow catfish. In addition, ycfad6 transcription was significantly reduced after a short-term (24-h) or long-term food deprivation (1-week) and then continued to decrease during refeeding, suggesting that nutritional states can affect the transcription of ycfad6, which further regulates the metabolism of HUFAs. Anyway, these fundamental findings provide basic references for further investigating evolutionary and physiological functions of the fad6 gene in yellow catfish as well as in other teleost fishes.
Research on axial compression performance test and bearing capacity calculation method of newly assembled hollow lattice wallboard
Authors: Liu Yunlin , Huo Shangwei , Wu Zhixin , Yang Dingguo , Ren Ke , Liu Jianhua , Wang Riguang
Published: August 2024

With the great development of the construction industry, prefabricated building components have been greatly developed. To study the compressive performance of the new wallboard, the axial compression performance test of six full-scale new lattice wallboards was carried out in this paper. The failure mode, axial pressure-displacement relationship curve, axial compression bearing capacity, and axial pressure-strain relationship of the wallboard were obtained through the experiments. This reveals the influence of the thickness of the concrete surface and the number of ribs on the performance of the wallboard. The test results show that the ultimate bearing capacity of the specimen increases with the increase of the thickness of the concrete surface layer with the same number of ribs. Specimen DW -30 increased by 4% over DW -20 and DW -50 increased by 41.6% over DW -30. The ultimate bearing capacity of the three-ribbed specimens was higher than that of the two-ribbed specimens for the same concrete face thickness, about 1.11 times that of the two-ribbed specimens. The concrete facing thickness and the number of ribs have a restraining effect on the deformation of the wallboard. Additionally, the calculation formula of axial bearing capacity of type latticed wallboard considering the influence of eccentric compression was proposed, which can provide a reference for engineering calculation.