bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning model for dissolved gas analysis: methodological review with a case in Hong Kong
Authors: Chan Philip TH , Chan Terry HW
Published: December 2024

Dissolved gas analysis is a valuable diagnostic tool used to monitor transformer health by analysing the gases dissolved in insulation oil. However, its practical application is hindered by the absence of a universal standard, leading to varied interpretations and implementations across different contexts. Scholars have turned to machine learning to advance DGA anomaly detection, but the existing literature prioritises model development over methodological rigour; issues such as dataset imbalance, appropriate evaluation metrics, and testing and validation procedures are often overlooked. This study addresses the existing gaps by critically reviewing the methodological steps involved in machine learning modelling with DGA datasets. The proposed design considerations are justified, and the analysis of the IEC TC 10 dataset and a dataset
from a Hong Kong company is enhanced. Using Python’s scikit-learn, over 18 combinations of datasets, data preprocessing techniques, and model architectures were assessed, and the random forest model (F1 = 0.88) and the support vector classifier with an RBF kernel (F1 = 0.87) were identified as the top-performing models, after applying Yeo-Johnson transformation. The models’ source code is available on the author’s GitHub repository.
NIPA: Historical Background, Status, and Prospects for Legislative Regulation
Authors: Tverezenko Olena
Published: December 2024

The purpose of this study is to analyze Ukrainian laws concerning intellectual property, with a focus on the legal regulation of the activities of the National Intellectual Property Authority. Additionally, the study aims to develop recommendations for their improvement and systematization to avoid duplication of legal norms in this area.To implement institutional reform within the intellectual property sector, the Law of Ukraine «On Amending Certain Legislative Acts of Ukraine Regarding the Establishment of a National Intellectual Property Authority» was adopted on June 16, 2020. This law introduced significant amendments to various Ukrainian laws. The changes affected the protection of rights to industrial designs, trademarks for goods and services, and layout designs of integrated circuits. Amendments also addressed the legal protection of geographical indications, inventions, and utility models. Additionally, the law revised regulations governing copyright and related rights, administrative services, and the effective management of property rights in these areas.An analysis of these amendments reveals that the legal provisions pertaining to the National Intellectual Property Authority (NIPA) are redundantly repeated across several specialized laws within the intellectual property domain.The article substantiates the inconsistency of the provisions of legislative acts in the part of regulating the activity of IP with the subjects of regulation of such laws, defined in their preambles.The author proposes many solutions to address the issue of duplicated legal norms overseeing the NIPA's operations: Codification of Ukrainian Intellectual Property Legislation (this could take the form of an Intellectual Property Code, an Industrial Property Code, or a Law on the Protection of Industrial Property); Passage of a Law National System of Legal Protection for Intellectual Property; Passage of a Law Specific to the National Intellectual Property Authority.In the author's view, the optimal approach to remedy the duplications evident in legislative provisions related to the NIPA — would involve removing these provisions from specialized laws and consolidating them into a singular regulatory act. This act should be formalized in the regulations governing the NIPA, as approved by a resolution of the Cabinet of Ministers of Ukraine.
Journalists as Reluctant Political Prophets
Authors: Tenenboim-Weinblatt Keren , Aharoni Tali , Baden Christian
Published: December 2024

This article examines the journalistic production of mediated political projections, defined as media narratives about uncertain futures in the political arena, such as anticipated outcomes and implications of elections. Despite the significance of prospective coverage in political journalism and its impact on political decision-making, there is limited understanding of journalists’ perceptions and textual expressions of political forecasting across various discursive forms, media types, and cultures. Drawing on interviews with Israeli journalists and a computational text analysis of election coverage in France, Israel, and the U.S., this study explores how journalists perceive, negotiate, and textually navigate political forecasting in their work. The findings reveal journalists’ deep ambivalence toward political forecasting and the resulting textual practices. We show how journalists attribute their engagement in forecasting to external pressures, while their reluctance stems from the inherent risks and challenges associated with political forecasting and its conflict with their journalistic identity. Journalists navigate this tension by incorporating projections into conventional factual reporting or using non-committal language. Except in data journalism, assessing the likelihood of political scenarios is uncommon. Although these patterns are observed across countries and media types, prospective coverage is more prevalent in interventionist and accommodative journalistic cultures, with the rhetoric of facticity and certitude more common in broadcast news. We argue that journalists’ reluctance to fully engage with the uncertainty of political futures limits their ability to effectively contribute to public decision-making processes in societies' navigation toward the future.
Children Health Information on Instagram: The Perception of Parents from Y and Z Generation
Authors: Arindita Ruvira , Hasna Safira , Zahradias
Published: December 2024

This study explores how Gen Y and Gen Z parents engage with children’s health information on Instagram, a popular topic on the platform. Using qualitative methods, researchers conducted in-depth interviews with parents who actively follow health- focused accounts. Findings show that parents’ content perception begins at the selection stage, with most preferring content created by doctors. They favor science-based, easily understood information and are drawn to doctors and influencers who communicate with empathy and clarity. Gen Z parents, typically with younger children, prioritize physical health, while Gen Y parents, often with older children, focus on psychological development. Gen Y is more open to longer text- based content, whereas Gen Z prefers audiovisual formats and still often refers to mom-influencers for children’s health information aside from doctors. The study suggests that health institutions should equip doctors with content creation skills, policymakers should encourage reliance on scientifically backed information, and health educators should personalize messages to connect effectively with each generation. Further studies should explore how fathers perceive health-related information from social media since the parents represented in this article are all mothers.
Dynamic downscaling of climate projections using WRF-CCSM4: future soil temperature predictions for the Arabian Peninsula and Kuwait
Authors: Alsarraf Hussain
Published: December 2024

This study employs the Weather Research and Forecasting (WRF) model to dynamically downscale climate projections from the Community Climate System Model version 4 (CCSM4) using 12 km and 4 km high grid resolutions. The performance of the WRF-CCSM4 configuration is evaluated against observational data from the automated weather observing systems of Kuwait (AWOSK). The analysis focuses on future predictions for maximum soil temperature during the summer months from May to September for the period 2050–2060. The findings indicate a projected increase in average soil temperatures of 1–3°C across the Arabian Peninsula and Kuwait. Notably, the results demonstrate that the 4-km high-resolution WRF domain, is more effective framework for accurate weather and climate predictions in this region. These insights underscore the importance of high-resolution modeling in understanding and mitigating the impacts of climate change, particularly in arid environments like Kuwait and the broader Arabian Peninsula.
Spatial distribution prediction of landslide susceptibility based on integrated particle swarm optimization
Authors: Zhang Qing
Published: December 2024

Landslide sensitivity prediction relies on multiple environmental factors, making it difficult to obtain accurate prediction results. In order to improve the prediction accuracy of regional landslide sensitivity, a landslide sensitivity spatial distribution prediction method based on integrated particle swarm optimization was studied in Lianhe Village, Jianfeng Town, Shizhong District, Leshan City, Sichuan Province. Based on the determination coefficient, the sensitivity of landslide influencing factors was analyzed, and the weights of the influencing factors were determined. A landslide sensitivity spatial distribution prediction model was established based on support vector machine. By introducing simulated annealing and mutation operations into the particle swarm algorithm, an integrated particle swarm algorithm was obtained to extract high weight features of landslide sensitivity space and generate landslide sensitivity prediction results. The experimental results show that the cumulative value (ACU) of this method for predicting landslide sensitivity is 0.91, which can accurately predict the spatial distribution of landslide sensitivity in the study area and has practical value.
Resilience and sustainability of entrepreneurial mindsets in Ghanaian youth: a five-year impact study of sports training programs
Authors: Nyanyofio Oscar Cornelius Nyanyo , Musah Karim , Nyawornota Vida Korleki , Tay Doris Akosua , Adamba Clement , Malete Leapetswe , McCole Daniel , Ocansey Reginald Tetteh-Ahumah
Published: December 2024

Introduction

Youth sports programs are recognized as effective tools for fostering entrepreneurial mindsets, resilience, and sustainable personal development. This study evaluates the long-term impact of the Africa Alliance for Partnerships (AAP) program on the academic and professional trajectories of its alumni, with a focus on sustained entrepreneurial skills and personal growth.

Methods

A structured survey was conducted among alumni who participated in the AAP program at least five years prior. Data on academic performance, career development, entrepreneurial activities, and personal experiences were collected and analyzed. Quantitative data were subjected to statistical tests, including regression and correlation analyses, while qualitative feedback underwent sentiment analysis.

Results

Findings indicate significant academic performance improvements and enhanced entrepreneurial skills among participants. The average skill application scores increased consistently from 2018 to 2023, with a strong positive correlation (r = 0.75) between skill application and academic improvement. Sentiment analysis revealed predominantly positive feedback, underscoring participant satisfaction with the program. Gender analysis showed no significant differences in outcomes, highlighting the program’s inclusivity.

Discussion

The AAP program successfully instilled entrepreneurial mindsets and resilience, sustained over five years. Key factors contributing to its success include mentorship, leadership training, and exposure to real-world challenges. These findings demonstrate the potential of sports-based youth development programs as sustainable models for fostering entrepreneurship and personal growth. Future research should explore additional external factors influencing outcomes and assess the scalability of such programs in diverse contexts.
Digital education training for teachers—Learnings from Austria
Authors: Hörmann Corinna , Kuka Lisa , Schmidthaler Eva , Sabitzer Barbara
Published: December 2024

The rapid evolution of digital technology has necessitated a shift in educational paradigms, particularly in teacher training and continuous professional development. This paper presents a study that explores Austrian teachers' attitudes toward digital education training and their preferences for in-service training modalities. Data were collected from a comprehensive survey involving about 600 Austrian secondary public school teachers and analyzed using quantitative and qualitative methods to reveal preferences and constraints in digital education in-service training, including the preferred modalities, the support required, and the teachers' motivations for engaging with training. Key findings from the study indicate that Austrian teachers generally have a positive perception of their autonomy in teaching digital education. Additionally, the study reveals that teachers are willing to participate in in-service training under specific conditions. This willingness is influenced by factors such as the flexibility of the training schedule, the provision of support resources, and the balance between professional obligations and personal time. The study highlights a broader trend toward flexibility and efficiency in in-service teacher training, acknowledging teachers' time constraints and the importance of maintaining a work-life balance. The findings suggest that flexible and supportive training environments can enhance teachers' engagement with digital education, ultimately benefiting their teaching practices and student outcomes. Overall, this study underscores the importance of adapting in-service teacher training to meet the needs of teachers, promoting a more effective integration of digital education.
Associations between non-insulin-based insulin resistance indices and diabetic nephropathy in patients with diabetes mellitus in US adults: a cross-sectional study of NHANES 1999–2018
Authors: Zhang Fan , Han Yan , Mao Yonghua , Li Wenjian
Published: December 2024

Objective

This study investigated the associations between non-insulin-based insulin resistance indices (METS-IR, TyG, TG/HDL, and TyG-BMI) and the risk of diabetic nephropathy (DN) in US adults with diabetes mellitus (DM).

Methods

This study was based on the 1999-2018 National Health and Nutrition Examination Survey (NHANES) database and included 6,891 patients with DM for cross-sectional analysis. Multivariate adjusted models and restricted cubic spline (RCS) models were employed to assess the association between the insulin resistance index and the risk of DN. Subgroup analyses were conducted to explore the impact of different population characteristics.

Results

The results indicated that higher quartiles of METS-IR, TyG, TG/HDL, and TyG-BMI were associated with a significantly increased risk of DN. After adjusting for multiple covariates, including gender, age, and race, the associations between these indices and the risk of DN remained significant, with corresponding odds ratios (ORs) of 1.51 (95% confidence interval [CI]: 1.29-1.76), 2.06 (95% CI: 1.77-2.40), 1.61 (95% CI: 1.38-1.88), and 1.57 (95% CI: 1.35-1.84), with all P-values less than 0.001. RCS analysis indicated a nonlinear relationship between these indices and the risk of DN. The TyG index exhibited a highly consistent association with the risk of DN in all models.

Conclusion

Non-insulin-based insulin resistance indices are significantly associated with the risk of DN. The TyG index is a superior tool for assessing the risk of DN. These indices can assist in identifying patients at risk of DN, thereby enabling the implementation of more effective preventive and therapeutic strategies.
Application of extracellular vesicles in diabetic osteoporosis
Authors: Jia Xiaopeng , Zhang Gongzi , Yu Deshui
Published: December 2024

As the population ages, the occurrence of osteoporosis is becoming more common. Diabetes mellitus is one of the factors in the development of osteoporosis. Compared with the general population, the incidence of osteoporosis is significantly higher in diabetic patients. Diabetic osteoporosis (DOP) is a metabolic bone disease characterized by abnormal bone tissue structure due to hyperglycemia and insulin resistance, reduced bone strength and increased risk of fractures. This is a complex mechanism that occurs at the cellular level due to factors such as blood vessels, inflammation, and hyperglycemia and insulin resistance. Although the application of some drugs in clinical practice can reduce the occurrence of DOP, the incidence of fractures caused by DOP is still very high. Extracellular vesicles (EVs) are a new communication mode between cells, which can transfer miRNAs and proteins from mother cells to target cells through membrane fusion, thereby regulating the function of target cells. In recent years, the role of EVs in the pathogenesis of DOP has been widely demonstrated. In this article, we first describe the changes in the bone microenvironment of osteoporosis. Second, we describe the pathogenesis of DOP. Finally, we summarize the research progress and challenges of EVs in DOP.
New PSO-GWO-based model for enhancing power quality in electrical networks interconnected with photovoltaic sources
Authors: Sanaei Mehdi , Akbari Hamidreza , Beheshtipour Zohreh , Mousavi Somayeh
Published: December 2024

This research introduces an innovative model to enhance power quality within electrical networks interconnected with photovoltaic (PV) sources. The central concern addressed in this study revolves around the impact of PV source power quality on local electric networks. This research endeavors to elucidate how achieving a more refined power pattern in electric networks is attainable by considering the power quality of PV sources. A hybrid Particle Swarm Optimization-Gray Wolf Optimization (PSO-GWO) algorithm is proposed to obtain optimal solutions. Empirical findings underscore the significant impact of Unified Power Quality Conditioners (UPQC) on social welfare, reinforcing the potential benefits of improving power quality. The results reveal that localized price reductions primarily drive the enhancement of social welfare, and this socioeconomic advantage outweighs improvements in sustainability metrics.
Exploring the potential mechanisms and future trends of industrial eco-efficiency: a case study of coastal China
Authors: Sun Yixuan , Zhang Teng , Zhang Baolei , Yin Le , Wang Jingjing
Published: December 2024

The industrial economy occupies a crucial position in China’s national economy, and industrial eco-efficiency (IEE) as a significant indicator of regional green development levels. Balancing the positive interaction between industrial economy and resource environment, and enhancing ecological efficiency in industrial development are vital for achieving sustainable regional economic development. This study measures the IEE of 115 cities in coastal China based on panel data of industrial resources and the environment factors. Subsequently, it further analyzes the influencing mechanisms and future trends of IEE. The results indicate that the overall IEE in coastal China is on an upward trend, with higher efficiency values in provinces and regions characterized by faster economic development and better environmental conditions. Significant changes in spatial patterns are observed, with the gaps between cities narrowing and a “multi-core” development model emerging. Factors such as per capita GDP, the ratio of industrial pollution control investment to GDP, innovation index, the proportion of foreign direct investment to GDP, and industrial labor productivity significantly positively influence IEE. In contrast, the proportion of industrial added value to GDP, urbanization rate, and the number of industrial enterprises exhibit notable negative inhibitory effects. Moreover, the interaction effect between industrialization level and other factors is most significant. In the future, IEE is expected to continue improving, although the sustainability of these changes appears weak. These findings reveal the potential impact mechanisms of resource consumption and environmental pollution caused by industrial activities on economic benefit output. This study provides a scientific basis for optimizing energy development layout, enhancing the comprehensive utilization of energy resources, and improving ecological compensation and protection mechanisms.
Comprehensive evaluation of AlphaMissense predictions by evidence quantification for variants of uncertain significance
Authors: Kurtovic-Kozaric Amina , Delalic Lejla , Mutapcic Belma , Comor Lejla , Siciliano Eric , Kiel Mark J.
Published: December 2024

Accurate variant classification is critical for genetic diagnosis. Variants without clear classification, known as “variants of uncertain significance” (VUS), pose a significant diagnostic challenge. This study examines AlphaMissense performance in variant classification, specifically for VUS. A systematic comparison between AlphaMissense predictions and predictions based on curated evidence according to the ACMG/AMP classification guidelines was conducted for 5845 missense variants in 59 genes associated with representative Mendelian disorders. A framework for quantifying and modeling VUS pathogenicity was used to facilitate comparison. Manual reviewing classified 5845 variants as 4085 VUS, 1576 pathogenic/likely pathogenic, and 184 benign/likely benign. Pathogenicity predictions based on AlphaMissense and ACMG guidelines were concordant for 1887 variants (1352 pathogenic, 132 benign, and 403 VUS/ambiguous). The sensitivity and specificity of AlphaMissense predictions for pathogenicity were 92% and 78%. Moreover, the quantification of VUS evidence and heatmaps weakly correlated with the AlphaMissense score. For VUS without computational evidence, incorporating AlphaMissense changed the VUS quantification for 878 variants, while 56 were reclassified as likely pathogenic. When AlphaMissense replaced existing computational evidence for all VUS, 1709 variants changed quantified criteria while 63 were reclassified as likely pathogenic. Our research suggests that the augmentation of AlphaMissense with empirical evidence may improve performance by incorporating a quantitative framework to aid in VUS classification.
Review of clinical and imaging findings in autoimmune glial fibrillary acidic protein astrocytopathy to aid in early diagnosis
Authors: Li Xiaomeng , Li Jiacun , Xu Han , Liu Xiaohui , Li Meilin , He Jingzhen , Xiu Jianjun
Published: December 2024

Objective

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a novel steroid sensitive autoimmune disease, without a diagnostic consensus. The purpose of this study was to improve early GFAP-A diagnosis by increasing awareness of key clinical characteristics and imaging manifestations.

Methods

Medical records of 13 patients with anti-GFAP antibodies in serum or cerebrospinal fluid (CSF) were reviewed for cross-sectional and longitudinal analysis of clinical and magnetic resonance imaging (MRI) findings.

Results

The predominant GFAP-A clinical manifestations are limb weakness/numbness and fever. GFAP-A has a propensity in the early stage for meningeal and leptomeningeal lesions on the brainstem surface, with a typical pattern of periventricular linear radial and leptomeningeal enhancement. The clinical manifestations and leptomeningeal enhancement were rapidly alleviated after treatment with high doses of corticosteroids or/and intravenous immunoglobulin, although, there are patients who may present with increased brain parenchymal lesions. On 3T MRI, the spinal cord demonstrated extensive longitudinal T2-weighted hyper-intensity, central distribution, and gray matter involvement. Optic nerve involvement in some patients was also noted with optic nerve swelling and abnormal enhancement. In addition to the classic reversible splenium of corpus callosum syndrome (type I), this study found the much rarer type II with diffusion restriction on DWI (Diffusion Weighted Imaging) in the corpus callosum. Positive anti-GFAP antibodies in serum or cerebrospinal fluid (CSF) are important for GFAP-A diagnosis with overlapping antibodies commonly noted. This study found anti-GM3 antibodies, a rare finding also previously reported.

Conclusion

This study correlates GFAP-A clinical and imaging features, noting a “delay” phenomenon between clinical manifestations, treatment response, and radiographic MRI findings. MRI T2-FLAIR brainstem hyperintensity and T2-FLAIR gadolinium enhanced images, and subtraction techniques were valuable for early lesion detection and accurate diagnosis.
AMBRA1 drives gastric cancer progression through regulation of tumor plasticity
Authors: Ye Liuqi , Lin Danlei , Zhang Wen , Chen Shiji , Zhen Yumiao , Akkouche Sara , Liang Xiaoxu , Chong Cheong-Meng , Zhong Hai-Jing
Published: December 2024

Background

Stomach adenocarcinoma (STAD) is an aggressive malignancy characterized by high tumor plasticity and heterogeneity. This study investigates the role of Autophagy and Beclin 1 Regulator 1 (AMBRA1) in regulating tumor plasticity in STAD progression.

Methods

Combined with clinical data, the pan-cancer analysis of AMBRA1 was performed to analyze the role of AMBRA1 in STAD. Western blot, Flow Cytometry (FCM) assay, trans-well assay, wound healing assay, MTT, Reactive Oxygen Species (ROS) assay, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and staining were performed to study the effects of AMBRA1 in AGS human gastric cancer cells. An AGS gastric cancer xenograft model was constructed to further verify the role of AMBRA1 in the development of STAD.

Results

AMBRA1 overexpression correlated with poor overall survival in STAD and was positively associated with T cell CD4+ infiltration. High AMBRA1 expression also indicated worse prognosis in patients with high cancer-associated fibroblast infiltration. AMBRA1 depletion suppressed STAD cell proliferation, migration, and invasion in vitro. Mechanistically, AMBRA1 knockdown induced G1/S cell cycle arrest and triggered cellular senescence through epigenetic alterations, including changes in H3K9me3 levels. AMBRA1 inhibition also sensitized STAD cells to chemotherapeutic agents. In vivo studies confirmed the tumor-suppressive effects of AMBRA1 loss, resulting in reduced tumor growth and increased cellular senescence.

Conclusions

Our findings uncover an oncogenic role for AMBRA1 in STAD. Targeting AMBRA1 may induce tumor cell senescence, apoptosis, and potentiate anti-tumor immunity, providing a rationale for developing AMBRA1-targeted precision therapies to improve clinical outcomes in STAD patients.
Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab
Authors: Lee Jaejun , Yoo Jae-Sung , Kim Ji Hoon , Lee Dong Yeup , Yang Keungmo , Kim Bohyun , Choi Joon-Il , Jang Jeong Won , Choi Jong Young , Yoon Seung Kew , Han Ji Won , Sung Pil Soo
Published: December 2024

Background

Programmed death-ligand 1 (PD-L1) expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells.

Methods

This study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023. PD-L1 expression on tumor tissues was assessed using the combined positive score (CPS) with cutoff values of 1 and 10, utilizing antibody clone 22C3 (Dako).

Results

The distribution of PD-L1 CPS included 24 patients with CPS <1, 33 patients with CPS 1–10, and 15 patients with CPS ≥10. Significant differences in overall survival (OS) were observed across the three groups, with CPS ≥10 showing the highest survival rates (p = 0.010). Patients with CPS ≥10 had better OS than those with CPS <10 (median OS 14.8 vs. 8.3 months, P = 0.046), and CPS ≥1 had better OS than CPS <1 (P = 0.021). For progression-free survival (mPFS), the CPS ≥10 group had the highest median PFS of 11.0 months among the three groups (P = 0.044). Objective response rates (ORR) were higher in the PD-L1 CPS ≥10 group than in the 1-10 and <1 group (53.3%, 27.3%, and 16.7%, respectively; P = .047). Multivariate analysis identified that PD-L1 expression ≥10 and ≥1 were associated with favorable outcomes regarding OS (hazard ratio [HR] 0.283, P = .027 and HR 0.303, P = .006, respectively).

Conclusions

Combined analysis of PD-L1 expression in malignant and tumor-infiltrating cells can be a promising biomarker for the prognosis of HCC patients treated with AB.
Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes
Authors: Campione Elena , Cosio Terenzio , Pistoia Enrico Salvatore , Artosi Fabio , Shumack Ruslana Gaeta , Borselli Cristiana , Rivieccio Antonia , Caputo Valerio , Favaro Marco , Sorge Roberto , Pica Francesca , Bianchi Luca , Gaziano Roberta
Published: December 2024

Introduction

Fungi, including Candida, may be a trigger or exacerbate psoriasis, especially in difficult to treat (DTT) areas, through the activation of IL-17/23 axis.

Methods

In this study, seventy patients with DDT psoriasis were enrolled to evaluate Candida species and/or other opportunistic fungi colonization rate at baseline (T0) and the impact of apremilast on fungal load, clinical outcome, serum cytokine levels and biochemical serum profile of patients after 16, 24 and 52 weeks of treatment.

Results

In our population, 33 (47%) patients were colonized by Candida spp. at baseline. In 24 (34%) individuals Candida was detected in the oral cavity while in the remaining 9 (13%) individuals the fungus was isolated from stool samples. Twenty subjects were colonized by only the species C. albicans, whereas in the remaining 13 a combination of two or more species (C. albicans plus non-albicans strains) was found in the oral cavity. Moreover, 27 (39%) patients were affected by onychomycosis. At 52 weeks, apremilast treatment induced a full recovery from Candida colonization in 83% of patients colonized with a single species of Candida (C. albicans); while in those co-infected by two or more Candida spp. induced a significant reduction (colony counts >10 CFU/mL) in fungal load was observed in comparison to baseline. Among patients with onychomycosis, 78% (21/27) of them presented a complete clinical resolution of nail psoriasis and concomitant nail infections. Finally, improvements in clinical scores i.e., PASI, NAPSI, DLQI, itch VAS, PAIN VAS, scPGA and sPGA-G and biochemical serum profile, as well as a significant decrease in serum IL-17A, TGF-β 1 and IL-10 levels (from 8.51 to 4.16 pg/mL; from 66.10 to 48.70 ng/mL and from 20.05 to 14 pg/mL, respectively) were observed in all patients.

Conclusions

Fungi may play a role in the psoriasis pathogenesis. Apremilast has been shown to ameliorate psoriasis signs and symptoms and counteract fungal overgrowth, probably by dampening inflammation, triggered by the fungal infections themselves. Thus, apremilast may represent an effective therapeutic approach in the treatment of DTT psoriasis and modulate the fungal colonization.
Decoding the prognostic landscape of LUAD: the interplay between N6-methyladenosine modification and immune microenvironment
Authors: Chen Quan , Wan Weijun , Zhao Qing , Li Juan , Xiong Yanli , Yuan Yuchuan , Tang Lu , Wu Xiaofeng , Xing Wei , Guo Wei , Lu Di , Ao Luoquan , Xu Xiang , Ao Xiang
Published: December 2024

Background

To determine the role of N6-methyladenosine (m6A) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD).

Methods

Consensus clustering was performed to identify the subgroups with distinct immune or m6A modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays. For experimental validation, the regulation of METTL3/m6A axis in the expression of candidate genes by RIP-qPCR assay in A549 and H460 cell lines. Co-culture experiments with human T cells were performed to evaluate the impact of METTL3 on the enhancement of anti-tumor immunity through in vitro experiments.

Results

We identified 282 m6A regulator genes and 955 immune-related genes, selecting seven key genes (SFTPC, CYP24A1, KRT6A, PTTG1, S100P, FAM83A, and ANLN) to develop a risk score model using Lasso regression. High-risk patients, determined by this model, exhibited poorer prognosis, increased immune infiltration, higher tumor mutational burden, more neoantigens, and elevated PD-L1 expression. These findings were validated by two independent databases and LUAD tissue microarrays. METTL3 was found to impact the mRNA expression of these genes, with METTL3 deficiency abolishing these interactions. Inhibition of METTL3 enhanced anti-tumor immunity, T cell activation, exhaustion, and infiltration in vitro.

Conclusion

This risk score system shows promise for prognostic prediction and the development of personalized treatment strategies for LUAD patients.
Predictors of breakthrough invasive fungal infections (BIFI) in pediatric acute leukemia: a retrospective analysis and predictive model development
Authors: Li Yan , Qu Lijun , Wang Jian , Chen Pingtian , Jiang Aoshuang , Liu Hongjun
Published: December 2024

Objective

This study aims to identify key risk factors associated with the development of breakthrough invasive fungal infections (BIFI) in pediatric acute leukemia patients to improve early detection and intervention strategies.

Method

A retrospective analysis was conducted on 160 pediatric patients with acute leukemia admitted to Anhui Provincial Children's Hospital between October 2018 and June 2022. The study evaluated the impact of various clinical parameters on BIFI risk using univariate and multivariable analyses, with data including patient demographics, treatment regimens, and infection outcomes. The predictive model was assessed using receiver operating characteristic (ROC) curve analysis, calibration plots, and decision curve analysis (DCA).

Result

Among the 160 pediatric acute leukemia patients, 34 (22.22%) developed BIFI. Univariate analysis identified longer durations of neutrophil deficiency (P < 0.001), broad-spectrum antibiotic use (P < 0.001), higher volumes of red blood cell transfusions (P = 0.001), and elevated C-reactive protein (CRP) levels (P < 0.001) as significant factors associated with BIFI. Multivariable analysis confirmed these as significant predictors, with odds ratios for neutrophil deficiency (OR = 1.38, 95% CI [1.15, 1.69]), antibiotic use (OR = 1.41, 95% CI [1.10, 1.84]), transfusions (OR = 2.54, 95% CI [1.39, 5.13]), and CRP levels (OR = 1.10, 95% CI [1.04, 1.17]). The model validation showed strong predictive performance with an AUC of 0.890 (95% CI: 0.828–0.952), good calibration (Brier score = 0.099), and demonstrated clinical utility across a range of risk thresholds.

Conclusion

The study highlights the importance of considering these key predictors in the management of pediatric acute leukemia patients to mitigate the risk of BIFI. Incorporating these factors into personalized treatment strategies could enhance early intervention, reduce infection rates, and improve overall patient outcomes.
Effect of carbonated water on cerebral blood flow in the frontal region: a study using near-infrared spectroscopy
Authors: Kosugi Wataru , Sumali Brian , Hamada Nozomu , Mitsukura Yasue
Published: December 2024

Introduction

Carbonated water (CarbW) affects the swallowing function associated with the action of the brainstem. In addition, CarbW ingestion promotes mean blood flow in the middle cerebral artery, which is associated with blood flow to the frontal and temporal lobes. In this milieu, studies regarding the effect of drinking CarbW on brain activity are of significance. In the present study, we compared the changes in cerebral blood flow in the frontal region before and after the ingestion of CarbW or uncarbonated water (SW).

Methods

Near-infrared spectroscopy was used to continuously measure the cerebral blood flow at 22 channels in the frontal region of 13 healthy young adults for 10 min before and after the ingestion of CarbW or SW. We statistically compared the changes in oxyhemoglobin concentration before and after the ingestion of CarbW or SW.

Results

Compared with that before CarbW ingestion, the oxyhemoglobin concentration in the left frontal region increased after CarbW ingestion. In particular, a significant increase (p < 0.05) was observed in the ch21 region. On the contrary, no marked increase or decrease in cerebral blood flow was observed after SW ingestion compared with that before ingestion.

Discussion

The activated part of the frontal region (ch21) corresponds to the vicinity of the orbitofrontal cortex, which is reportedly activated by rewarding stimuli. In addition, as the orbitofrontal cortex is located at the terminal end of the reward pathway of the mesocortical system, CarbW ingestion might have acted on the dopaminergic reward pathway of the mesocortical system.
The impact of COVID-19 on accelerating of immunosenescence and brain aging
Authors: Müller Ludmila , Di Benedetto Svetlana
Published: December 2024

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has profoundly impacted global health, affecting not only the immediate morbidity and mortality rates but also long-term health outcomes across various populations. Although the acute effects of COVID-19 on the respiratory system have initially been the primary focus, it is increasingly evident that the virus can have significant impacts on multiple physiological systems, including the nervous and immune systems. The pandemic has highlighted the complex interplay between viral infection, immune aging, and brain health, that can potentially accelerate neuroimmune aging and contribute to the persistence of long COVID conditions. By inducing chronic inflammation, immunosenescence, and neuroinflammation, COVID-19 may exacerbate the processes of neuroimmune aging, leading to increased risks of cognitive decline, neurodegenerative diseases, and impaired immune function. Key factors include chronic immune dysregulation, oxidative stress, neuroinflammation, and the disruption of cellular processes. These overlapping mechanisms between aging and COVID-19 illustrate how the virus can induce and accelerate aging-related processes, leading to an increased risk of neurodegenerative diseases and other age-related conditions. This mini-review examines key features and possible mechanisms of COVID-19-induced neuroimmune aging that may contribute to the persistence and severity of long COVID. Understanding these interactions is crucial for developing effective interventions. Anti-inflammatory therapies, neuroprotective agents, immunomodulatory treatments, and lifestyle interventions all hold potential for mitigating the long-term effects of the virus. By addressing these challenges, we can improve health outcomes and quality of life for millions affected by the pandemic.
The central regulatory effects of acupuncture in treating primary insomnia: a review
Authors: Yao Lin , Liu Yanze , Li Mengyuan , Zheng Haizhu , Sun Mengmeng , He Min , Zhong Zhen , Ma Shiqi , Huang Haipeng , Wang Hongfeng
Published: December 2024

Chronic insomnia has the potential to significantly impact physical well-being, occupational performance, and overall quality of life. This review summarizes the clinical and basic research on the central regulatory mechanism of acupuncture in treating primary insomnia (PI), aiming to explore the clinical effectiveness and possible mechanism of acupuncture in treating PI. The currently available drugs for insomnia exhibit notable adverse effects and tend to induce dependence. Empirical evidence from clinical investigations has demonstrated that acupuncture has a favorable safety profile while substantially enhancing the sleep quality of individuals diagnosed with PI. The combination of acupuncture and medication has been shown to augment the therapeutic efficacy of medication while reducing the dosage and mitigating the occurrence of unwanted effects. A review of the current clinical and basic research on the effects of acupuncture on central alterations in PI patients revealed that acupuncture exerts a regulatory influence on the functional activity of brain regions implicated in cognitive and emotional processes. Additionally, acupuncture has been found to impact metabolite levels and circadian clock gene expression and enhance inflammatory responses and energy metabolism. Notably, a single acupuncture intervention had a modulatory effect on functional brain regions similar to that of cumulative acupuncture. The current clinical trials on acupuncture have been limited in scale, and basic research has focused on a single objective. With the continuous progress of brain research, extensive clinical randomized controlled trials of high quality can be combined with various neuroimaging technology modalities. Moreover, different targets and pathways can be explored through basic research. This may serve to enhance the understanding of the fundamental central nervous system mechanisms involved in the efficacy of acupuncture in treating PI.
Neuraxial biomechanics, fluid dynamics, and myodural regulation: rethinking management of hypermobility and CNS disorders
Authors: Frost Nicole , Barclay S. Jade
Published: December 2024

Individuals with joint hypermobility and the Ehlers-Danlos Syndromes (EDS) are disproportionately affected by neuraxial dysfunction and Central Nervous System (CNS) disorders: such as Spontaneous Intracranial Hypotension (SIH) due to spinal cerebrospinal fluid (CSF) leaks, Upper Cervical Instability (UCI; including craniocervical or atlantoaxial instability (CCI/AAI)), Occult Tethered Cord Syndrome (TCS), Chiari Malformation (CM) and Idiopathic Intracranial Hypertension (IIH). The neuraxis comprises the parts of the nervous system (brain, nerves, spinal cord) along the craniospinal axis of the body. Neuraxial tissue includes all tissue structures that comprise, support, sheath, and connect along the neuraxis and peripheral nerves. Altered mechanical loading or vascular supply of neural structures can adversely impact neural health and conductivity, with local and remote effects on inflammation, venous congestion, and muscle control. With EDS characterized by altered structure of the connective tissues found throughout the body including the neural system, altered mechanical properties of the central nervous system (CNS) and its surrounding tissue structures are important considerations in the development and diagnostics of these CNS disorders, as well as response to therapeutic interventions. Experts have identified a need for neuraxial curriculum in medical education and hypermobility-adapted treatment approaches in pain management, neurosurgery, anesthesiology, hematology, gastrointestinal surgery, dermatology, cardiology, dentistry, gastroenterology, allergy/immunology, physical therapy, primary care, radiology and emergency medicine. This paper reviews the interactions between neuraxial biomechanics and pathology related to CNS disorders seen commonly with EDS. First, we provide a concise synthesis of the literature on neuraxial kinematics and fluid dynamics. We then discuss the interplay of these biomechanics and their involvement in clinically-relevant diagnoses and overlapping symptom presentations, modeling physiological reasoning to highlight knowledge gaps, support clinical decision-making, improve multidisciplinary management of hypermobility-associated complexity, and add weight to the call for medical education reform.
Characteristics of peripheral immune response induced by large-vessel occlusion in patients with acute ischemic stroke
Authors: Ma Ling , Sun Bin , Fan Chenliu , Xiao Juan , Geng Maomao , Liu Jie , Jiang Runze , Jiang Yang , Liu Dianwei
Published: December 2024

Introduction

Despite improvements in the treatment of acute ischemic stroke (AIS), some patients still suffer from functional impairments, indicating the poor understanding of pathophysiologic process of AIS. Inflammation plays an important role in the pathophysiology of AIS. The purpose of the study was to investigate the peripheral inflammation in different subtypes of AIS.

Methods

Here, retrospective data from AIS with large vessel occlusion (LVO) and small vessel occlusion (SVO), and healthy controls, were initially analyzed. Then, flow cytometry was performed to evaluate the levels of peripheral naïve and memory T-cells. Finally, we characterized the T cell receptors (TCR) repertoire using high-throughput sequencing.

Results

Elevated levels of leukocytes, neutrophils, and neutrophil-to-lymphocyte ratio (NLR), and decreased levels of lymphocytes were found in LVO group than that in SVO group, which were correlated with the severity of LVO. In addition, higher percentages of both effector memory (Tem) and central memory (Tcm) T cells, and lower percentage of naïve T cells in CD4+ and CD8+ T cells, were found in LVO group than that in SVO and healthy groups. Moreover, impaired TCR diversity, and different abundances of V-J gene combinations and amino acid sequences, were found in LVO as compared with healthy group, which would be potential biomarkers for LVO diagnosis.

Discussion

In conclusion, AIS with LVO can rapidly induce peripheral immune response, which provides new insight into the understanding of pathophysiology of AIS.
A comparative study of wavelet families for schizophrenia detection
Authors: Sathiya E. , Rao T. D. , Kumar T. Sunil
Published: December 2024

Schizophrenia (SZ) is a chronic mental disorder, affecting approximately 1% of the global population, it is believed to result from various environmental factors, with psychological factors potentially influencing its onset and progression. Discrete wavelet transform (DWT)-based approaches are effective in SZ detection. In this report, we aim to investigate the effect of wavelet and decomposition levels in SZ detection. In our study, we analyzed the early detection of SZ using DWT across various decomposition levels, ranging from 1 to 5, with different mother wavelets. The electroencephalogram (EEG) signals are processed using DWT, which decomposes them into multiple frequency bands, yielding approximation and detail coefficients at each level. Statistical features are then extracted from these coefficients. The computed feature vector is then fed into a classifier to distinguish between SZ and healthy controls (HC). Our approach achieves the highest classification accuracy of 100% on a publicly available dataset, outperforming existing state-of-the-art methods.