bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safe dynamic optimization of automatic generation control via imitation-based reinforcement learning
Authors: Zhang Zhiyuan , Wu Yongjun , Hao Zhenkun , Song Minghui , Yu Peipei 
Published: September 2024

IntroductionThe increasing penetration of distributed generation (e.g., solar power and wind power) in the energy market has caused unpredictable disturbances in power systems and accelerated the application of intelligent control, such as reinforcement learning (RL), in automatic generation control (AGC). However, traditional RL cannot ensure constraint safety during training and frequently violates the constraints (e.g., frequency limitations), further threatening the safety and stability of grid operation.MethodsTo address the safety issue, we propose a novel safe RL framework that combines expert experiences with the RL controller to achieve imitation-based RL. This method allows an initialized safe policy by imitating expert experiences to prevent random explorations at the beginning. Specifically, we first formulate the AGC problem mathematically as a Markov decision process. Then, the imitation mechanism is developed atop a soft actor–critic RL algorithm.Results and discussionFinally, numerical studies are conducted with an IEEE 39-bus network, which show that the proposed method satisfies the frequency control performance standard better and improves the RL training efficiency.
Intralesional gene expression profile of JAK-STAT signaling pathway and associated cytokines in Leishmania tropica-infected patients
Authors: Hadifar Shima , Masoudzadeh Nasrin , Heydari Hossein , Mashayekhi Goyonlo Vahid , Kerachian Mohammadali , Daneshpazhooh Maryam , Sadeghnia Ali , Tootoonchi Nasim , Erfanian Salim Reza , Rafati Sima , Harandi Ali M. 
Published: September 2024

BackgroundThe JAK-STAT signaling pathway is a central cascade of signal transduction for the myriad of cytokines in which dysregulation has been implicated in progression of inflammatory and infectious diseases. However, the involvement of this pathway in human cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica warrants further investigation.MethodsThis study sought to investigate differential gene expression of several cytokines and their associated jak-stat genes in the lesions of L. tropica-infected patients byquantitative Real-Time PCR. Further, the expression of five inhibitory immune checkpoint genes was evaluated.ResultsResults showed that the gene expression levelsof both Th1 (ifng, il12, il23) and Th2 (il4, il10) types cytokines were increased in the lesion of studied patients. Further, elevated expression levels of il35, il21, il27 and il24 genes were detected in the lesions of CL patients. Notably, the expression of the majority of genes involved in JAK/STAT signaling pathway as well as checkpoint genes including pdl1, ctla4 and their corresponding receptors was increased.ConclusionOur finding revealed dysregulation of cytokines and related jak-stat genes in the lesion of CL patients. These results highlight the need for further exploration of the functional importance of these genes in the pathogenesis of, and immunity to, CL.
Immune and inflammatory insights in atherosclerosis: development of a risk prediction model through single-cell and bulk transcriptomic analyses
Authors: Chen Xiaosan , Zhang Zhidong , Qiao Gang , Sun Zhigang , Lu Wei 
Published: September 2024

BackgroundInvestigation into the immune heterogeneity linked with atherosclerosis remains understudied. This knowledge gap hinders the creation of a robust theoretical framework essential for devising personalized immunotherapies aimed at combating this disease.MethodsSingle-cell RNA sequencing (scRNA-seq) analysis was employed to delineate the immune cell-type landscape within atherosclerotic plaques, followed by assessments of cell-cell interactions and phenotype characteristics using scRNA-seq datasets. Subsequently, pseudotime trajectory analysis was utilized to elucidate the heterogeneity in cell fate and differentiation among macrophages. Through integrated approaches, including single-cell sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning techniques, we identified hallmark genes. A risk score model and a corresponding nomogram were developed and validated using these genes, confirmed through Receiver Operating Characteristic (ROC) curve analysis. Additionally, enrichment and immune characteristic analyses were conducted based on the risk score model. The model’s applicability was further corroborated by in vitro and in vivo validation of specific genes implicated in atherosclerosis.ResultThis comprehensive scRNA-seq analysis has shed new light on the intricate immune landscape and the role of macrophages in atherosclerotic plaques. The presence of diverse immune cell populations, with a particularly enriched macrophage population, was highlighted by the results. Macrophage heterogeneity was intricately characterized, revealing four distinct subtypes with varying functional attributes that underscore their complex roles in atherosclerotic pathology. Intercellular communication analysis revealed robust macrophage interactions with multiple cell types and detailed pathways differing between proximal adjacent and atherosclerotic core groups. Furthermore, pseudotime trajectories charted the developmental course of macrophage subpopulations, offering insights into their differentiation fates within the plaque microenvironment. The use of machine learning identified potential diagnostic markers, culminating in the identification of RNASE1 and CD14. The risk score model based on these biomarkers exhibited high accuracy in diagnosing atherosclerosis. Immune characteristic analysis validated the risk score model’s efficacy in defining patient profiles, distinguishing high-risk individuals with pronounced immune cell activities. Finally, experimental validation affirmed RNASE1’s involvement in atherosclerotic progression, suggesting its potential as a therapeutic target.ConclusionOur findings have advanced our understanding of atherosclerosis immunopathology and paved the way for novel diagnostic and therapeutic strategies.
Logistic regression model for predicting risk factors and contribution of cerebral microbleeds using renal function indicators
Authors: Liu Xuhui , Pan Zheng , Li Yilan , Huang Xiaoyong , Zhang Xiner , Xiong Feng 
Published: September 2024

BackgroundThe brain and kidneys share similar low-resistance microvascular structures, receiving blood at consistently high flow rates and thus, are vulnerable to blood pressure fluctuations. This study investigates the causative factors of cerebral microbleeds (CMBs), aiming to quantify the contribution of each risk factor by constructing a multivariate model via stepwise regression.MethodsA total of 164 hospitalized patients were enrolled from January 2022 to March 2023 in this study, employing magnetic susceptibility-weighted imaging (SWI) to assess the presence of CMBs. The presence of CMBs in patients was determined by SWI, and history, renal function related to CMBs were analyzed.ResultsOut of 164 participants in the safety analysis, 36 (21.96%) exhibited CMBs and 128 (78.04%) did not exhibit CMBs, and the median age of the patients was 66 years (range: 49–86 years). Multivariate logistic regression identified hypertension (OR = 13.95%, 95% CI: 4.52, 50.07%), blood urea nitrogen (BUN) (OR = 1.57, 95% CI: 1.06–2.40), cystatin C (CyC) (OR = 4.90, 95% CI: 1.20–22.16), and urinary β-2 microglobulin, (OR = 2.11, 95% CI: 1.45–3.49) as significant risk factors for CMBs. The marginal R-square (RM2) was 0.25. Among all determinants, hypertension (47.81%) had the highest weight, followed by UN (11.42%). Quasi-curves plotted using the bootstrap method (999 times) showed good agreement between the predictive model and actual observations.ConclusionHypertension, BUN, urinary β-2 microglobulin, CyC were risk factors for CMBs morbidity, and controlling the above indicators within a reasonable range will help to reduce the incidence of CMBs.
Transcriptomics-based anti-tuberculous mechanism of traditional Chinese polyherbal preparation NiuBeiXiaoHe intermediates
Authors: Wang Nan , Ma Qianqian , Zhang Junxian , Wang Jie , Li Xiaojun , Liang Yan , Wu Xueqiong 
Published: September 2024

BackgroundIntegrated traditional Chinese medicine and biomedicine is an effective method to treat tuberculosis (TB). In our previous research, traditional Chinese medicine preparation NiuBeiXiaoHe (NBXH) achieved obvious anti-TB effects in animal experiments and clinical practice. However, the action mechanism of NBXH has not been elucidated.MethodPeripheral blood mononuclear cells (PBMCs) were collected to extract mRNA and differentially expressed (DE) genes were obtained using gene microarray technology. Finally, GEO databases and RT-qPCR were used to verify the results of expression profile.ResultAfter MTB infection, most upregulated DE genes in mice were immune-related genes, including cxcl9, camp, cfb, c4b, serpina3g, and ngp. Downregulated DE genes included lrrc74b, sult1d1, cxxc4, and grip2. After treatment with NBXH, especially high-dose NBXH, the abnormal gene expression was significantly corrected. Some DE genes have been confirmed in multiple GEO datasets or in pulmonary TB patients through RT-qPCR.ConclusionMTB infection led to extensive changes in host gene expression and mainly caused the host’s anti-TB immune responses. The treatment using high-dose NBXH partially repaired the abnormal gene expression, further enhanced the anti-TB immunity included autophagy and NK cell-mediated cytotoxicity, and had a certain inhibitory effect on overactivated immune responses.
Long-term effects of siponimod on cardiovascular and autonomic nervous system in secondary progressive multiple sclerosis
Authors: Constantinescu Victor , Haase Rocco , Akgün Katja , Ziemssen Tjalf 
Published: September 2024

BackgroundSiponimod, a second-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, represents an important therapeutic choice for active secondary progressive multiple sclerosis (SPMS). Besides the beneficial immunomodulatory effects, siponimod impacts cardiovascular function through S1PR1 modulation. Short-term vagomimetic effects on cardiac activity have proved to be mitigated by dose titration. However, long-term consequences are less known.ObjectivesThis study aimed to investigate the long-term impact of siponimod on cardiac autonomic modulation in people with SPMS (pwSPMS).MethodsHeart rate variability (HRV) and vascular hemodynamic parameters were evaluated using Multiple Trigonometric Regressive Spectral analysis in 47 pwSPMS before siponimod therapy and after one, three, six and 12 months of treatment. Autonomic activation tests (tilt test for the sympathetic and deep breathing test for the parasympathetic cardiac modulation) were performed at each examination.ResultspwSPMS preserved regular cardiovascular modulation responses during the autonomic tests reflected in the variation of several HRV parameters, such as RMSSD, pNN50, total power of HRV, high-frequency and low-frequency bands of the spectral domain or hemodynamic vascular parameters (Cwk, Zao, TPR, MAP) and baroreflex sensitivity (BRS). In the long-term follow-up, RMSSD, pNN50, total power, BRS and CwK presented a significant decrease, underlining a reduction of the parasympathetic and a shift towards sympathetic predominance in cardiac autonomic modulation that tends to stabilise after 1 year of treatment.ConclusionDue to dose titration, the short-term effects of siponimod on cardiac autonomic modulation are mitigated. The long-term impact on cardiac autonomic modulation is similar to fingolimod. The autonomic activation tests showed normal cardiovascular responses during 1-year follow-up in pwSPMS, confirming the safety profile of siponimod. Further research on autonomic function could reveal whether the observed sympathetic activation is a compensatory response to S1P signaling intervention or a feature of the disease, while also shedding light on the role of S1PR modulation in MS.
Isoliensinine suppressed gastric cancer cell proliferation and migration by targeting TGFBR1 to regulate TGF-β-smad signaling pathways
Authors: Hu Jinda , Dai Shangming , Yuan Mengqin , Li Fengjiao , Xu Shuoguo , Gao Lichen 
Published: September 2024

BackgroundGastric cancer (GC) ranks as the fifth most prevalent cancer globally, and its pronounced invasiveness and propensity to spread provide significant challenges for therapy. At present, there are no efficacious medications available for the treatment of patients with GC. Isoliensinine (ISO), a bisbenzylisoquinoline alkaloid, was isolated from Nelumbo nucifera Gaertn. It possesses anti-tumor, antioxidant, and other physiological effects. Nevertheless, there is currently no available study on the impact of ISO on GC, and further investigation is needed to understand its molecular mechanism.MethodsISO target points and GC-related genes were identified, and the cross-target points of ISO and GC were obtained. We then examined cross-targeting and found genes that were differentially expressed in GCs. Kaplan-Meier survival curves were used to screen target genes, and the STRING database and Cytoscape 3.9.1 were used to construct protein-protein interactions and drug-target networks. In addition, molecular docking studies confirmed the interactions between ISO screen targets. Finally, in vitro tests were used to establish the impact of ISO on GC cells.ResultsThrough bioinformatics research, we have identified TGFBR1 as the target of ISO in GC. In addition, we noticed a substantial inhibition in GC cell proliferation, migration, and invasion activities following ISO treatment. Moreover, we noticed that ISO treatment effectively suppressed TGF-β-induced epithelial-mesenchymal transition (EMT) and activation of the TGF-β-Smad pathway. Furthermore, we discovered that siTGFBR1 nullified the impact of ISO on TGF-β-triggered migration, invasion, and activation of the TGF-β-Smad pathway.ConclusionOur research suggests that ISO specifically targets TGFBR1 and regulates the TGF-β-Smad signaling pathway to suppress the proliferation and migration of GC cells.
Medicinal plants diversity among the oromo community in heban-arsi district of Ethiopia used to manage human and livestock ailments
Authors: Nuro Geritu , Tolossa Ketema , Arage Mahlet , Giday Mirutse 
Published: September 2024

IntroductionMedicinal plants are commonly employed mainly due their accessibility, affordability and potency. However, medicinal plants and the associated knowledge are disappearing at an alarming rate due to natural and anthropogenic causes and thus a need for their proper documentation conservation. This study was performed to document traditional knowledge related to use of medicinal plants in Heban-Arsi district, West-Arsi Zone, Oromia Regional State, Ethiopia.MethodsInterviews were conducted with 185 informants to identify medicinal plants used in traditional therapies in the study area. Informant consensus factor (ICF), rank order priority (ROP) values were computed, and preference ranking exercises were performed to assess the relative importance of medicinal plants. Descriptive and inferential statistics were used to measure and compare medicinal plants knowledge between social groups.ResultsA total of 120 medicinal plants were identified for being used to treat different human and animal illnesses in the study area. Most of the medicinal plants (76.4%) were uncultivated ones obtained from different habitats. Leaf was the most frequently used plant part constituting 62.6% of preparations. Oral was the most commonly used route of remedy administration (46%) in treating diseases. Gastrointestinal ailments category had the highest ICF value (0.83). In the study area, the highest rank order priority (ROP) values were recorded for Dombeya torrida (J.F. Gmel.), Artemisia absinthium L., Balanites aegyptiaca (L.) Del., Combretum pisoniiflorum Klotzsch) Engl., Celtis africana Burm. f, Ocimum gratissimum L. and Lagenaria sp. for their uses against snake poison, tuberculosis, liver disorder, stomachache, tuberculosis, febrile illness and liver disorder, respectively, each scoring a value of 100. Significant differences in medicinal plant use knowledge were recorded between male and female informants of different educational level, age and experience. Anthropogenic factors were the primary threats to medicinal plants in the area.ConclusionThe study area was found to be rich in medicinal plants that are useful in treating a wide range of human and animal illnesses. In future pharmacological and phytochemical investigations, priority needs to be given to medicinal plants of the highest ROP values and those that were reported against ailment categories scoring the highest ICF values.
Emerging psychosocial factors and work overload perceptions of Mexican university teachers and students working and studying from home during the COVID-19 pandemic
Authors: Quezada Díaz Belem , Hindrichs Imke , Castellanos Simons Doris 
Published: September 2024

IntroductionIn Mexico, academic activities during the COVID-19 pandemic were conducted from home for over 2 years. Especially during the initial months of the pandemic, the lockdown conditions necessitated a reorganization and a new understanding of social dynamics. Therefore, this study aimed to explore the perceptions of university students and teachers regarding emerging psychosocial factors that either encouraged or hindered work and/or study from home during confinement, as well as their perceptions of work overload. Furthermore, the differences between students and teachers in the studied variables were analyzed.MethodA predominantly quantitative, cross-sectional, and correlational study was conducted with 108 participants (42.6% university teachers; 57.4% graduate or postgraduate students) who filled out an online questionnaire encompassing two open-ended inductors to identify the positive and negative aspects of working or studying from home and their frequency of perceptions, the COVID-19 Work Overload from Home Scale (ESTC-COVID-19), and questions about the hours per day devoted to different activities. The open responses were categorized by two independent groups of the research team; the emerging categories were then consensually agreed upon and further transformed into dummy and continuous variables. These variables and the results of the ESTC-COVID-19 were analyzed with SPSS 19 using Pearson's correlation coefficient, the Chi-squared test, and Student's t-test. The results identified 9 positive and 10 negative emerging psychosocial factors attributed to at least 10% of the sample's open answers. In addition, work overload correlated negatively with the emerging factor of “Making better use of time” and positively with “Work, school, and/or domestic activities overload;” moreover, students perceived more work overload than teachers.DiscussionDifferences between students and teachers were observed in the following psychosocial factors: “Self-management,” “Comfort,” and “Enjoying home” (as positive factors) and “Domestic work” and “Interruptions, distractors, noise” (as negative factors), with students generally reporting more discomfort than teachers. The study analyzes these differences in relation to the demands and nature of the study and work activities undertaken by both groups, as well as the previous training of the skills and the resources required to carry them out.
The interconnection between social media addiction, alexithymia and empathy in medical students
Authors: Ursoniu Sorin , Bredicean Ana-Cristina , Serban Costela Lacrimioara , Rivis Ioana , Bucur Adina , Papava Ion , Giurgi-Oncu Catalina 
Published: September 2024

IntroductionThis study explores whether high alexithymia values correlate with low levels of empathy, while also trying to identify potential connections with social media addiction.MethodsWe hypothesized that alexithymia mediates the relationship between social media addiction and empathy levels in a sample of undergraduate students. The study population consisted of 649 medical students in the 4th/5th/6th University year, recruited between March and May 2021. For this assessment, we employed three psychometric instruments: the Toronto Empathy Questionnaire (TEQ), the Social Media Addiction Scale-Student Form (SMAS-SF), and the Toronto Alexithymia Scale (TAS-20). A pathway analysis investigated alexithymia as a mediator between social media addiction and the degree of empathy in medical undergraduates. Sobel’s test and the Baron and Kenny approach were used for testing mediation.ResultsThe TEQ total mean score was 48.76 ± 5.65, while the TAS-20 total mean score was 47.71 ± 11.49. Further analysis of the TAS-20 scale scores showed that 21.42% of students had possible alexithymia, while 14.02% had clear alexithymia. The SMAS-SF total mean score was 73.20 ± 14.59. None of the students reported levels consistent with major social media addiction. The mediated effect of the TAS-20 is about 1.3 times larger than the direct effect of the SMAS-SF on TEQ.DiscussionWe found a significant negative correlation between empathy and alexithymia in medical students. Alexithymia was a mediator between social media addiction and empathy. Therefore, we recommend further efforts to identify potential levels of alexithymia in medical students, in order to successfully develop tailored interventions aimed at increasing their emotional awareness.
Eye care service utilization and associated factors among adults in Debre Berhan Town, North Shewa, Ethiopia, 2023
Authors: Bekele Matiyas Mamo , Shumye Abebech Fikade , Tegegn Melkamu Temeselew 
Published: September 2024

IntroductionGlobally, the utilization of eye care services varies widely, ranging from 18 to 90%. Low utilization of eye care services can lead to delayed detection of vision problems. However, there are limited data on the proportion of eye care service utilization and its associated factors in Ethiopia at the community level.ObjectiveThe objective of this study was to determine the proportion of eye care service utilization and its associated factors among adults in Debre Birhan town, North Shewa, Ethiopia.MethodsUsing a multistage sampling method, a community-based cross-sectional study was conducted on 960 adults in Debre Birhan town from 8 May to 8 June 2023. Binary logistic regression was performed. Variables with a p-value of less than 0.05 were considered significant.ResultsA total of 940 study participants participated, resulting in a response rate of 97.9%. The mean age of the participants was 54.67 years (SD ± 8.69). The proportion of good-level eye care service utilization was found to be 32.98% [95% confidence interval (CI): 29.97, 35.99]. Factors positively associated with good-level eye care service utilization included older age [adjusted odds ratio (AOR) = 1.58, 95%CI: 1.00, 2.51], higher educational status (AOR = 2.25, 95%CI: 1.25, 4.06), high family monthly income (AOR = 8.70, 95%CI: 4.99,15.18), awareness of regular eye checkups (AOR = 1.77, 95%CI: 1.15, 2.73), a history of eye disease (AOR = 2.57, 95%CI: 1.77,3.74), health insurance (AOR = 1.99, 95% CI: 1.34, 2.95), and history of spectacle use (AOR = 1.94, 95%CI:1.34, 2.80).ConclusionThe study revealed that the proportion of good-level eye care service utilization was low. Older age, higher educational status, high family monthly income, awareness of regular eye checkups, a history of eye disease, health insurance, and history of spectacle use were significantly associated with a good level of eye care service utilization.