bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide association and expression analyses of programmed cell death associated genes provide novel insight into therapeutic target in differentiated thyroid cancer
Authors: Zhang Qinnan , An Nan , Li Xueqing , Zhang Panpan , Yang Qian , Pan Fanfan , Wang Kai , Zha Bingbing
Published: February 2024

BACKGROUND
The incidence of differentiated thyroid cancer (DTC) has been increasing in recent years with high risk of recurrence and metastasis. Inducing programmed cell death (PCD) is one of the most promising therapy in the development of anti-DTC agents. However, which genes play the key roles in DTC remain unclear.
METHODS
Based on 14 kinds of PCD patterns, we leveraged Summary-data-based Mendelian randomization (SMR) analysis, integrating DTC GWAS (Cases comprised of 649 patients had histological proven) with expression quantitative trait loci (eQTL) from blood in eQTLGen and verifed in thyroid tissues of GTExV8 to explore the causality between different PCD genes and DTC in genomic and transcriptomic backgrounds. scRNA-seq analysis was linked to individual genetic variation to reveal cell specificity in peripheral blood mononuclear cells (PBMCs) and tumor microenvironment, respectively. Furthermore, we also analyzed the relationship of susceptibility genes and immune infiltration and clinicl correlation with the pathological stages.
RESULTS
The results suggested that 55 PCD genes in blood exhibited association with DTC, 48 of which were enriched in PBMCs. 13 genes were found in thyroid tissue cis-eQTL, 12 of which could be verified in tumor microenvironment. Among these, 6 genes consistently replicated in both blood and thyroid tissues were proposed preferentially. These genes were associated with 3 distinct PCD patterns: Apoptosis (NFATC4, RPS3 and TM2D1), Lysosome-dependent cell death (CTNS and GCC2), Autophagy (TPCN2). Besides, the expression levels of RRPS3 and TM2D1 genes in elderly (> 65 years old) patients with thyroid cancer were significantly lower than those in young. And it was worth noting that the expression levels of CTNS, GCC2, TM2D1 and TPCN2 genes gradually decreased with the increase of T stage.
CONCLUSIONS
This study uncovered several PCD related genes protecting against the development of DTC. These results provide a basis for further exploring the regulatory mechanisms of PCD on DTC, which might open up new therapy target for DTC based on inducing in programmed cell death.
Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system
Authors: Hung Chi-Feng , Chiu Wei-Che , Chen Jia-Cih , Chuang Wu-Chang , Wang Su-Jane
Published: February 2024

Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague‒Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1β, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1β/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.
Assessment of validity and reliability of the Feedback Quality Instrument
Authors: Amirzadeh Sahar , Rasouli Davood , Dargahi Helen
Published: February 2024

Background: The purpose of the research was to investigate the psychometric features of the Feedback Quality Instrument (FQI) in medical students, emphasizing the instrument's utility as a tool for evaluating the quality of feedback provided in clinical contexts and the importance of performing so for medical trainees.
Methods and Material: The Persian version of the FQI was evaluated for content validity through a focus group of medical education experts. The questionnaire's face, content, and construct validity were assessed using Confirmatory Factor Analysis, internal consistency, and inter-rater reliability. The questionnaire was revised and pilot-tested, with 110 medical students completing the final version. The data was analyzed using AMOS26.
Results:The content validity index equaled 0.88(>0.79). The content validity ratio which represents the proportion of participants who agreed on a selected item was 0.69(>0.42). For reliability, Cronbach alpha was equaled to 0.98.
Conclusions: The Persian version of the Feedback Quality Instrument (FQI) was found to be valid and reliable in assessing feedback quality in medical students, providing valuable insights for other institutions. Future research could compare the predictive value of this test with other measures of feedback quality with educational and clinical outcomes.
Identification of mucosal microbiome-host gene interactions in ulcerative colitis patients
Authors: Kim Namjoo , Gim Jeong-An , Lee Beom Jae , Choi Byung il , Yoon Hee Sook , Kim Won Shik , Kim Seung Han , Joo Moon Kyung , Park Jong-Jae
Published: February 2024

The role of gut microbiota in clinical applications, such as markers for diagnosis, prognosis prediction, and therapeutic agents in inflammatory bowel disease, is still unclear. Here, we analyzed the mucosal microbiome, which can discriminate between the active state of moderate-to-severe ulcerative colitis (UC) and normal state, and explored the correlations between microbes and host genes by integrating 16s RNA sequencing and RNA sequencing in the colonic mucosa of UC patients and healthy controls. Correlation analyses were performed between the mucosal microbiome and host gene expression, followed by a network analysis. The DEG results showed that 28 and 18 genes were expressed at higher levels in the UC and normal groups, respectively. GSEA revealed 1,857 gene sets to be enriched in the UC group. In UC, we found a higher abundance of taxa such as genera Lactobacillus and Neisseria and less abundance of species such as Bacteroides coprocola, Bacteroides phlebeius, and Parabacteroides merdae. Significant positive gene-taxa correlations were observed between Lactobacillus and REG4 (Spearman rho = 0.86), Bacteroides coprocola and NBR1 (Spearman rho = 0.75), Bacteroides plebeius and COLCA2 (Spearman rho = 0.77), and Parabacteroides merdae and UTX-AS1 (Spearman rho = 0.74). Our results provide the basis for the role of microbiota in colonic mucosa in the initial development of UC, and the integrated analysis of the host microbiome and genes can serve as a biomarker for diagnosis and treatment target in UC patients.
Heterarchical modelling of comminution for rotary mills: Part I — Particle crushing along streamlines
Authors: Bisht Mukesh Singh , Guillard François , Shelley Paul , Marks Benjy , Einav Itai
Published: February 2024

Rotary mills aim to effectively reduce the size of particles through a process called comminution. Modelling comminution in rotary mills is a challenging task due to substantial material deformation and the intricate interplay of particle kinematics of segregation, mixing, crushing, and abrasion. Existing particle-based simulations tend to provide predictions that cannot cope with the large number of particles within rotary mills, their wide range of sizes, and the physics dictating the crushing of individual particles. Similarly, there is currently no deterministic modelling means to determine the evolving population of particle sizes at any point in time and space within the mill. The aim of this two-part contribution is to address these gaps by advancing a framework for a novel stochastic comminution model for rotary mills, which has a well-defined deterministic continuum limit and can cope with arbitrarily large numbers of particles. This work describes the basic physics and structure of the new model within a heterarchical framework for ball and autogenous grinding mills. The primary focus of this Part I paper is to develop a computational model for the integration of motion of material along streamlines inside a mill. Coupled to this process is the kinetic physics dictating particle crushing. In a subsequent work, Part II, segregation and mixing will be added to this model such that realistic behaviour from the mill can be observed.
Effect of Household Diet Quality on Health Outcomes in Nigeria
Authors: Jerumeh Tolulope Rachael
Published: February 2024

This study examines the impact of household diet quality on health outcomes in Nigeria, utilizing 2018/2019 General Household Survey data. Employing various techniques, including Minimum Dietary Diversity for Women (MDDW), Food Group Diversity Score (FGDS), and Probit model, the research assesses diet composition and its alignment with dietary guidelines. Findings indicate prevalent consumption of grains, plantains, roots, tubers, meat, fish, poultry, other vegetables, and pulses, while dark green leafy vegetables and eggs are less consumed. The average Global Dietary Resilience (GDR) score is 10.5, reflecting halfway adherence to WHO recommendations. Urban households exhibit a slightly higher GDR score (10.66) than rural counterparts (10.50). Urban diets, rich in health-protective foods, also feature elements that contribute to Non-Communicable Diseases (NCDs). The study establishes that enhanced diet quality significantly reduces NCD risk in adults and lowers stunting prevalence in under-five children. It emphasizes the necessity for policies and interventions to elevate household diet quality in Nigeria. Targeted efforts are recommended to promote healthier dietary choices, particularly in urban areas with elevated NCD prevalence, through interventions and campaigns.
Bronchoscopic management of bronchopleural fistula using free fat pad transplant with platelet-rich plasma: A case study
Authors: Wang YuHsiang , Huang Hsu Chih , Lin Frank Cheau Feng
Published: February 2024

Background
A bronchopleural fistula (BPF) occurs when an abnormal connection forms between the bronchial tubes and pleural cavity, often due to surgery, infection, trauma, radiation, or chemotherapy. The outcomes of both surgical and bronchoscopic treatments frequently prove to be unsatisfactory.
Case presentation
Here, we report a case of successful bronchoscopic free fat pad transplantation combined with platelet-rich plasma, effectively addressing a post-lobectomy BPF. Contrast-enhanced chest tomography revealed pleural thickening with heterogeneous consolidations over the right upper and middle lobes, indicative of destructive lung damage and bronchiectasis. The patient underwent thoracoscopic bilobectomy of the lungs. During surgery, severe adhesions and calcification of the chest wall and lung parenchyma were observed. The entire hilar structure was calcified, presenting challenges for dissection, despite the assistance of energy devices. Bronchoscopic intervention was required, during which two abdominal subcutaneous fat pads were retrieved.
Conclusion
This innovative approach offers promise in the management of BPF and signals potential advancements in enhancing treatment efficacy and patient recovery.
Gender-specific effect of dietary fatty acids on nonalcoholic fatty liver disease
Authors: Shi Jiejun , Chen Jianhua
Published: February 2024

Background
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic disease worldwide. Dietary fatty acids are tightly associated with the development of NAFLD while in-depth large-scale clinical researches are few.
Methods
A retrospective case-control study was conducted based on the data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Weighted multivariable logistic regression, smooth curve fitting and forest plot were used to describe the relationships between dietary fatty acids, related ratios and NAFLD. Subgroup analysis focused on the influence of gender, weight and age on the forementioned relationships.
Results
A total of 2470 adult participants were included in this study. Logistic regression analysis showed that dietary fatty acids were positively associated with NAFLD (odd ratio (OR) and 95% confidence interval (CI) > 1 and P < 0.05) except for polyunsaturated fatty acid. Subgroup analysis stratified by age stage and weight grade revealed that forementioned association was significant only in the age group of 37–55 and obese individuals. Ratios of unsaturated-to-saturated fatty acids and polyunsaturated-to-monounsaturated fatty acids showed protective effects on the onset and steatosis severity of NAFLD only in males based on stratified logistic regression analysis (all the OR [95% CI] < 1 and P < 0.05) and smooth curve fittings.
Conclusions
The findings suggest that adjustment of dietary fatty acids can be used as a preventive strategy for NAFLD. Increasing the proportion of unsaturated fatty acids in the diet, especially polyunsaturated fatty acids, is promising to prevent NAFLD in middle-aged obese men.
Sustainable precast composite deep beams including concrete with partial replacement (50%) of recycled coarse aggregate
Authors: Shakir Qasim M. , Alghazali Asmaa F.
Published: February 2024

Three new sustainable models of a hybrid deep beam have been proposed in this work, which are the curved (CRV) and the arched (ARC1) and the modified arched (ARC2) in addition to the conventional (HRL) hybrid model that uses recycled coarse aggregates (RCA) instead of natural aggregates. The specimens indicate that steel fiber concrete (SFC) is used in high stress concentration areas and sustainable concrete is used in other areas. In relation to the parameters, the effects of hybridization types and inclined stirrups have all been studied. Results revealed that the failure capacity was increased by 8%, 22%, 21%, and 22%, for the for hybrid models respectively. On the other hand, the specimen (CTRL-SFC) showed a 19% enhancement. Regarding the flexural toughness, enhancement in 13%, 39%, 34%,71% for the hybrid models respectively compared to the non-hybrid model (CTRL-R50).The respective enhancement for the specimen (CTRL-SFC) was 52%.For the effective stiffness, results showed small range of enhancement (1.5-9)%. It is evident that the specimens' internal reinforcement detailing is adequate to stop the semi-diagonal mode of failure, which is an extremely brittle mode of failure. Furthermore, a replacement rate of up to 50% does not significantly affect the overall response. Moreover, The results of the tests indicated that the inclined alignment of the stirrups prevented diagonal cracking more than their vertical alignment. The proposed curved and arched models may be used with multi-concentrated loads, prestressed beam, precast walls. The proposed models aimed to produce lightweight / sustainable /low cost /high performance precast deep beams with compared to the horizontal hybrid model.
Analysis of Wear Characteristics of Hydrodynamic Seals During Start- up Using 3D Fractal Characterization and Study of Opening Performance Degradation Mechanism
Authors: Bi Enzhe , Li Shuangxi , Zhai Zhixing , Huang Baiqi , Liu Xinghua , Zhang Jiangteng
Published: February 2024

To investigate the degradation mechanism of the opening performance of hydrodynamic seals during multiple start-ups, a model was proposed to analyze the wear characteristics during the start-up process, and an experimental study was conducted. It has been discovered that the state evolution of the hydrodynamic seal during the single start-up process occurs in five stages. The main factor that influences the deterioration of the initial performance of hydrodynamic seals during multiple start-ups is the decrease in the depth of the root groove. To prevent the deterioration of the initial performance of the hydrodynamic seal, it is essential to minimize processing errors in groove depth and reduce the residence time during the mid-speed and mid-load stages of the starting process.
Next-Generation Sequencing-Based Evaluation of the Actionable Mutational Landscape in Solid Tumors: the “MOZART” Prospective Observational Study
Authors: Schettini Francesco , Sirico Marianna , Loddo Marco , Williams Gareth H , Hardisty Keeda-Marie , Scorer Paul , Thatcher Robert , Rivera Pablo , Milani Manuela , Strina Carla , Ferrero Giuseppina , Ungari Marco , Bottin Cristina , Zanconati Fabrizio , Manzini Nicolò , Aguggini Sergio , Tancredi Richard , Fiorio Elena , Fioravanti Antonio , Scaltriti Maurizio , Generali Daniele
Published: February 2024

Background
The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine mutations’ type, frequency and actionability and potential correlations with PD-L1 expression.
Methods
304 adult patients with heavily-pretreated metastatic cancers treated between 01/2019-03/2021 were recruited. The CLIA-/UKAS-accredit Oncofocus® assay targeting 505 genes was used on newly-obtained or archived biopsies. Chi-square, Kruskal-Wallis and Wilcoxon rank-sum test were used where appropriate. Results were significant for p < 0.05.
Results
A total of 237 tumors (78%) harbored actionable mutations. Tumors were positive for PD-L1 in 68.9% cases. The median number of mutant genes/tumor was of 2.0 (IQR: 1.0–3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%) and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found between PD-L1, ESCAT, age, sex and tumor mutational status. Sixty-two patients underwent targeted treatment, with 37.1% obtaining objective responses.
Conclusions
We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment.
Fractional order Jacobi wavelet-based numerical analysis of fractal-fractional multi-pantograph delay differential equation with variable coefficients
Authors: Singh Deepak , Verma Sag Ram
Published: February 2024

In this study, the fractal-fractional Caputo and Caputo-Fabrizio derivatives are used to formulate the fractal-fractional model of multi-pantograph delay differential equations with variable coefficients. The wavelet method is constructed to provide a numerical solution by using fractional-order Jacobi wavelets. This methodology relies on the operational matrix for fractal-fractional integration of fractional order Jacobi wavelets and the collocation method. We defined pseudo code and stability analysis of the proposed approach for the given model. The error analysis and comparison of the numerical results are also shown in the tables and graphs for the three illustrative examples. In the proposed methods, the data are obtained on different values of fractal \((\nu)\) and fractional \((\mu,\phi)\) parameters and it is noteworthy to point out that the classical case is recovered for \(\mu=1\) and \(\nu=1\).
Screening of potential hub genes involved in Kidney Wilms tumor via bioinformatics analysis and experimental validation
Authors: Zeng Qiang , Liu Tingting , Qin Lilu , Wang Chen , Peng Guangbei , Liu Zhong , Tao Junfeng
Published: February 2024

Background:
Wilms tumor (WT) is the most common pediatric embryonal tumor. Improving patient outcomes requires advances in understanding and targeting the multiple genes and cellular control pathways, but its pathogenesis is currently not well-researched. We aimed to identify the potential molecular biological mechanism of WT and develop new prognostic markers and molecular targets by comparing gene expression profiles of Wilms tumors and fetal normal kidneys.
Methods:
We performed differential gene expression analysis on Wilms tumor transcriptomic data from the GEO database and TARGET database. GO, KEGG, and GSEA pathways were utilized for the biological functional analysis. 9 of 24 hub genes were identified had prognosis-related by univariate Cox regression analysis. Nine genes underwent LASSO regression analysis to enhance the predictive capability of the model. Finally, The key hub genes were validated in the TARGET-WT datasets, and cell function experiments were conducted to identify the gene's function in the WiT-49 cell.
Results:
The enrichment analysis revealed that DEGs were significantly involved in the regulation of angiogenesis and regulation of cell differentiation. 24 DEGs were identified through PPI networks and the MCODE algorithm, and 9 of 24 genes were related to WT patients' prognosis. EMCN and CCNA1 were identified as key hub genes, and related to the progression of WT. Functionally, over-expression of EMCN and CCNA1 knockdown inhibited cell viability, proliferation, migration, and invasion of Wilms tumor cells.
Conclusions
Our study suggests that EMCN and CCNA1 as prognostic signatures associated with the progression of WT.
OTULIN-related conditions: Report of a new case and review of the literature using GenIA
Authors: Caballero-Oteyza Andrés , Crisponi Laura , Peng Xiao P. , Wang Hongying , Mrovecova Pavla , Olla Stefania , Siguri Chiara , Marnissi Farida , Jouhadi Zineb , Aksentijevich Ivona , Grimbacher Bodo , Proietti Michele
Published: February 2024

OTULIN encodes an eponymous linear deubiquitinase (DUB), which through the regulation of M1-Ub dynamics, is essential for controlling inflammation as a negative regulator of the canonical NF-𝛋B signaling pathway. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative effects. In this manuscript, we report the identification of a novel homozygous missense mutation, p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype. We go on to systematically review the literature for OTULIN-related human disease phenotypes by using the GenIA databaseto collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. We show how GenIA facilitates comprehensive synthesis across genotypic, phenotypic, and mechanistic data, enabling a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and the drafting of diagnostic and management guidelines; but it also identifies outstanding knowledge gaps and raises additional questions for future investigation.
Choroidal and Retinal Changes in Patients with Allergic Rhinoconjunctivitis
Authors: Akcal Omer , Suleymanzade Matin , Isik Burcu , Ersoz Mehmet Giray
Published: February 2024

PURPOSE
Allergic rhinoconjunctivitis (ARC) is an allergic upper respiratory tract disease characterized by sneezing, runny nose, nasal congestion and ocular and nasal itching due to inflammation of the nasal and conjunctival mucosa. There are no studies evaluating both the choroidal and retinal areas in ARC patients. Our objective was to evaluate patients with ARC at the time of diagnosis and before initiating treatment using Optical Coherence Tomography (OCT).
METHODS
This prospective cross-sectional study included 30 patients with ARC who presented to the Pediatric Allergy & Immunology Outpatient Clinic and 30 healthy control individuals. OCT scans were captured with Cirrus HD OCT-5000 (Carl Zeiss, Jena, Germany) in the enhanced depth imaging (EDI) mode.
RESULTS
Of the study population, 66.7% (n=20) of patient group and 56.6% (n=17) of control group were female. The mean age was 13±2.3 and 13.9±1.8 years in the patient and control groups, respectively. The temporal subfoveal choroidal thickness was statistically significantly thinner in ARC patients with asthma (p=0.032). A robust negative correlation was found between minimum ganglion cell-inner plexiform layer (GCIPL) thickness and allergic eosinophil count (AEC) in patients with ARC (r: -0.551, p<0.0001).
CONCLUSION
In our study, the GCIPL thickness was lower in ARC patients. Similarly, although it did not reach statistical significance, the minimum GCIPL thickness was lower in our patient group with asthma compared to those without asthma. Our results suggest that multiple allergen sensitization and elevated eosinophils may influence GCIP thickness. However, both choroidal and retinal tissue might be impacted during chronic follow-up. Further studies are needed to support these findings.
Graph Fourier transform for spatial omics representation and analyses of complex organs
Authors: Chang Yuzhou , Liu Jixin , Jiang Yi , Ma Anjun , Yeo Yao Yu , Guo Qi , McNutt Megan , Krull Jodran , Rodig Scott J. , Barouch Dan H. , Nolan Garry , Xu Dong , Jiang Sizun , Li Zihai , Liu Bingqiang , Ma Qin
Published: February 2024

Spatial omics technologies are capable of deciphering detailed components of complex organs or tissue in cellular and subcellular resolution. A robust, interpretable, and unbiased representation method for spatial omics is necessary to illuminate novel investigations into biological functions, whereas a mathematical theory deficiency still exists. We present SpaGFT (Spatial Graph Fourier Transform), which provides a unique analytical feature representation of spatial omics data and elucidates molecular signatures linked to critical biological processes within tissues and cells. It outperformed existing tools in spatially variable gene prediction and gene expression imputation across human/mouse Visium data. Integrating SpaGFT representation into existing machine learning frameworks can enhance up to 40% accuracy of spatial domain identification, cell type annotation, cell-to-spot alignment, and subcellular hallmark inference. SpaGFT identified immunological regions for B cell maturation in human lymph node Visium data, characterized secondary follicle variations from in-house human tonsil CODEX data, and detected extremely rare subcellular organelles such as Cajal body and Set1/COMPASS. This new method lays the groundwork for a new theoretical model in explainable AI, advancing our understanding of tissue organization and function.
Analysis of the interaction of antimalarial agents with Plasmodium falciparum Glutathione Reductase through molecular mechanical calculations
Authors: Ferreira F. H. do C , Pinto L. R. , Oliveira B. A. , Daniel L. V. , Navarro M. , Delgado G. Y. Sánchez
Published: February 2024

Malaria remains a significant global health challenge, with emerging resistance to current treatments necessitating the development of novel therapeutic strategies. P. falciparum Glutathione Reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarial drugs and dual drugs combining aminoquinoline derivatives with GR inhibitors using molecular docking and molecular dynamics simulations. Our findings reveal promising interactions between PfGR and antimalarial drugs, with the naphthoquinone Atovaquone (ATV) demonstrating particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity compared to reference inhibitors, suggesting their efficacy in inhibiting PfGR. Insights into their interaction mechanisms and structural dynamics are described. Overall, this research provides valuable insights into the potential of targeting PfGR and encourages further exploration of its role in the mechanisms of action of antimalarial drugs, including dual drugs, to enhance antiparasitic efficacy.
Analysis and Suppression of Offshore Wind Power Broadband Oscillation Based on HVDC Transmission Technology
Authors: Yang Zhangbin , Li Gang , Ding Yiwei , Peng Daixiao , Kaikai Zou , Ruan Lin
Published: February 2024

This paper explores the dynamics of large-scale offshore wind farms comprised of full-power variable frequency wind turbines, interconnected with flexible HVDC (High Voltage Direct Current) converter stations. These systems are susceptible to broad frequency oscillations due to the rapid response characteristics of power electronic devices, potentially compromising their operational safety and stability under various conditions. To mitigate the impact of these oscillations on offshore wind turbines and the connected systems, the study first outlines the structure and operational mode of the offshore wind power electronic system with flexible HVDC transmission. It then analyzes the mechanisms underlying these broad frequency oscillations. Subsequently, the paper presents a model construction and stability analysis for wind farms and flexible HVDC systems. It specifically focuses on offshore wind power systems with flexible HVDC transmission based on symmetric mono-polar topology, involving multiple branches and multiple wind farm access points. The research includes an in-depth oscillation analysis, supported by real-world case studies, demonstrating that strategically optimized control and protection strategies can effectively reduce the oscillation risks associated with wind farms connected through flexible HVDC systems, thereby ensuring their safe and stable operation.
Features of molecular self-assembled helix peptide nanotubes based on some amino acids molecules and their dipeptides: molecular modelling studies
Authors: Bystrov Vladimir
Published: February 2024

The paper considered the structural and dipole moments features of some amino acids that are important in the formation of the di-peptides and peptide nanotubes on their basis. The influence of the features of their chirality (left L and right D) and the alpha-helix conformations of amino acids also were taken into account. In particular, amino acids with aromatic rings were considered, such as phenylalanine (Phe/F), and branched-chain amino acids (BCAAs) Isoleucine (Ile/I), Leucine (Leu/L), as well as corresponding dipeptides based on them. On their basis, the features and properties of dipeptide structures and peptide nanotubes (PNTs) were investigated using computational molecular modeling and quantum-chemical semi-empirical calculations. Their polar, piezoelectric and photoelectronic properties and features were studied in details. The results of calculations of dipole moments and polarization, as well as piezoelectric coefficients and band gap width, for different types of helical peptide nanotubes are presented. The calculated values of the chirality indices of various nanotubes are given, depending on the chirality of the original dipeptides - the results obtained are consistent with the law of changes in the type of chirality as the hierarchy of molecular structures becomes more complex. Calculations were also carried out on the influence of water molecules in the internal cavity of nanotubes on their physical properties. Comparison of the results of these calculations by various computational chemistry methods with the available experimental data were also be given.
Diagnostic performance of a rapid immunochromatographic test for the simultaneous detection of antibodies to Theileria equi and Babesia caballi in horses and donkeys
Authors: Jongejan Frans , Du Cheng , Papadopoulos Elias , Blanda Valeria , Bella Santina , Canella Vincenza , Guercio Annalisa , Vicari Domenico , Tirosh-Levy Sharon , Steinman Amir , Baneth Gad , Keulen Sanna , Hulsebos Iris , Berger Laura , Wang Xiaojun
Published: February 2024

Background
Equine piroplasmosis is caused by two tick-borne protozoan parasites, Theileria equi and Babesia caballi, which are clinically relevant in susceptible horses, donkeys, and mules. Moreover, equine piroplasmosis significantly constrains international trading and equestrian events. Rapidly diagnosing both parasites in carrier animals is essential for implementing effective control measures. Here, a rapid immunochromatographic test for the simultaneous detection of antibodies to T. equi and B. caballi was evaluated using samples from horses and donkeys collected in Greece, Israel and Italy. The results were compared with a competitive ELISA for detecting antibodies to both parasites using the same panel of samples.
Methods
Blood samples were collected from 255 horses and donkeys. The panel consisted of 129 horses sampled at four locations in northern Greece, 105 donkeys at four locations in Sicily and 21 horses at two locations in Israel. The rapid test and the cELISA were performed according to the manufacturer's instructions, and the results were subjected to a statistical analysis.
Results
The immunochromatographic test provided a result within 15 minutes and can be performed in the field, detecting both pathogens simultaneously. The overall coincidence rate between the rapid test and the cELISA for detecting antibodies against T. equi was 93% and 92.9% for B.caballi. The rapid test's sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for T.equi were above 91.5%. Sixteen samples were positive for both parasites in the rapid test and eight in the cELISA. Either test had no significant association between T. equi and B. caballi detection. The detection rates of both parasites were significantly higher in Italy than in Greece or Israel and in donkeys than in horses. The agreement for T.equi between the results of both tests was high in Greece (93.8%) and Italy (95.2%) and moderate in Israel (76.2%). For B.caballi, the specificity and NPV of the rapid test were high (94.2% and 98.3%, respectively), although the sensitivity and PPV were moderate (69.2% and 39.1%, respectively) due to the small sample size. However, for B. caballi, the sensitivity was higher with the rapid test.
Conclusions
The rapid test detected T.equi and B.caballi simultaneously in the field, potentially replacing laborious cELISA testing and is recommended for import/export purposes. The test can also be helpful for the differential diagnosis of clinical cases since seropositivity may rule out equine piroplasmosis since it does not indicate current or active infection.
Clinical Features of Chronic Tibial Osteomyelitis: A Single-center Retrospective Study of 282 Cases in Xinjiang, China
Authors: Huang Xiaoxia , Chen Jiahan , Li Qian , Liu Tao , Zhao Yan , Teng Yong
Published: February 2024

Objective:This study aims to provide theoretical basis for treatment and prevention of osteomyelitis by investigating and analyzing clinical features and pathogen distribution among 282 patients with chronic tibial osteomyelitis.
Methods:A total of 282 patients with chronic tibial osteomyelitis from January 1, 2012 to January 1, 2022 in the First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed. All data were collected from electronic medical record (EMR) system including demographics, etiology, risk factors, osteomyelitis location and clinical classification.
Results:Farmers, students, unemployed and retirees accounted for a relatively large proportion of the 282 patients. There were 233 males and 49 females with a gender ratio of 4.75:1. The average age was 40.21±15.68 years and was mainly concentrated in 41-50 years, specifically, the mean age of females was slightly older than that of males. Education level was mostly primary and secondary school education, and illiteracy. Risk factors of chronic tibial osteomyelitis included history of smoking and drinking, history of multiple repeated surgeries, and impaired immunity. Frequent clinical symptoms were in the order of pain, local swelling,pus discharge and skin ulceration. Among all inflammatory markers, proportion of positive results were 30.85%, 59.93% and 53.90% for white blood cell (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), respectively. Positive rate of pathogenic microorganism culture was low and the three most common bacteria were Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli). The most frequent site of infection was middle tibia. According to Cierny-Mader osteomyelitis classification, the most common types were type IIIA, IVA and IIA.
Conclusion:Number of visits due to chronic osteomyelitis increased year by year, with young and middle-aged male farmers and low education level as the main groups. Smoking and drinking were two considerable risk factors that should be attached to a great importance. No significant increase was found in inflammatory markers and lower positive rate of pathogenic microorganism culturewas observed. Multi-drug resistant bacteria were common and S. aureus remained the most frequent pathogen. Elevated ESR had certain diagnostic value for osteomyelitis. Type III and type IV osteomyelitis accounted for a large proportion which posed great challenges for clinical diagnosis and treatment.
Feasibility Analysis of Line of Sight (LOS) Underwater Wireless Optical Communications (UWOCs) via Link Budget
Authors: Zayed M. Mokhtar , Shokair Mona , Elagooz Salah , Elshenawy Hamed
Published: February 2024

Optical Wireless Communications (OWCs) are capable of handling large data rate in the Internet of Underwater Things (IoUT) at low latency to be suitable for real time image and video applications. This paper presents communication link feasibility via link budget to determine the link communication range for three types of line-of-sight link configurations: point to point, diffused and modulating retro reflector link. The main aim of this paper studies a more realistic power link budget which is developed to take into account the following: LED Photo Source Lambertian radiation model, Beer Lambert pass loss model that includes absorption and scattering effects of water types, Spherical wave propagation model, photo detector which is modeled by active area model, transmitter projection optics (PO) gain and receiver collection optics (CO) gain. Moreover, this paper considers the effects of aquatic channels ‘scattering and absorption by using IM-DD OOK intensity modulation direct detection, LED and LD –PS based transmitter and SiPM-PD based receiver. The impact of different underwater environment, transmitter and receiver parameters will be investigated on the communication link range. Its range on the order of tens of meters could be achieved by the three link configurations. It is concluded from the analysis; line of sight point to point provides more communication range than diffused line of sight. Diffused line of sight is used when it is required to multicast from a node to several nodes. Modulating retro reflector provides moderate communication range and it is used when one party has more resources than the other one on the communication link. For medium distances, is determined by up to a hundred meter by placing multiple relay nodes between source node and destination node. The communication range is increased as increasing the active physical area of photodetector and transmitted power. The communication range in both clear sea water and clear ocean water is higher turbid water which is less since optical water suffers from higher attenuation. By using the multi hop concept, extended communication link range can be achieved.
Cost of integrated immunization campaigns in Nigeria and Sierra Leone: bottom-up costing studies
Authors: Boonstoppel Laura , Moi Flavia , Banks Christina , Sibeudu Florence , Obodoechi Divine , Borces Kyle , Onwujekwe Obinna , Brenzel Logan
Published: February 2024

Background
To improve the efficient use of scarce resources, low- and middle-income countries and development partners are increasingly encouraged to deliver multiple vaccines and other interventions in a single integrated campaign. However, little is known regarding the cost of delivering vaccines through integrated campaigns, and the extent to which efficiencies are achieved. To fill this evidence gap, we estimated the cost of integrated immunization campaigns in Nigeria and Sierra Leone, and the potential savings from integration.
Methods
We conducted a retrospective ingredients-based costing study from a payer perspective of a campaign held in 2019 in Sierra Leone with measles-rubella vaccine and oral polio vaccine, during which nutrition supplements were also offered in part of the country, and yellow fever campaigns held in three states in Nigeria in 2019 and 2020, where in one state (Anambra) meningococcal A vaccines were co-delivered. We collected data from 108 health facilities, all relevant administrative levels, and implementing partners. We estimated the full financial and economic cost of each campaign, the average unit cost of delivery, as well as the cost by activity and resource type. We also estimated the cost savings from integration in Anambra state by modelling out the cost of the alternative of two standalone campaigns.
Results
The average financial delivery cost was $0.34 per dose in Sierra Leone, and the economic cost was $0.73 per dose. In Nigeria, the financial cost per dose was $0.29–$0.35 across the three states, and the economic cost per dose was $0.62–$0.85. Facilities and wards delivering more doses achieved a lower financial and economic unit cost of delivery, demonstrating evidence of economies of scale. We estimated that Anambra may have saved at least $1,204,133 in financial resources by integrating yellow fever and meningitis A vaccine delivery, amounting to $0.17 per dose delivered. When including opportunity costs, the economic cost saving was estimated at $0.34 per dose delivered.
Conclusions
The study offers evidence on what it costs to deliver integrated campaigns, and shows that integrated delivery is likely to result in significant cost savings. Where high delivery volumes can be achieved, integrated campaigns can benefit from economies of scale. The findings can be used to inform planning and budgeting for immunization campaigns in low- and middle-income countries.
The durability of different anchoring points and anchoring types in the left ventricle in an ex-vivo porcine model
Authors: Bjursten Henrik , Wierup Per , Koul Sasha , Settergren Magnus , Götberg Matthias , dencker magnus
Published: February 2024

Objective: Various percutaneous approaches are under development to perform transcatheter treatment of mitral valve disease, where many try to anchor in the left ventricle. This pilot study investigates the durability of different anchoring points and types in the left ventricle. Anchoring was tested in three different locations: the head of the papillary muscle, the lateral wall of the ventricle, and the apex of the ventricle. In addition, two different anchoring types were tested: PTFE sutures that mimicked mitral valve repair and a de novo developed 5 mm helix.
Results: The lowest numerical strain/compliance during the first cycle was seen for the head of papillary muscle anchoring (both surgical and helix). Migration of strain limits over 300 cycles was seen for all locations. Numerically, the lowest migration was for the helix in the papillary muscle. PTFE in the head of the papillary muscle is standard practice in mitral valve repair and was used as a reference in the present study. The anchoring that gave the most consistent results was a helix in the papillary muscle, while other anchoring points showed larger compliance and/or migration.
Clinical impact and cost-consequence analysis of ePlex® Blood Culture Identification Panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial
Authors: Caspar Yvan , Deves Arthur , Richarme Claire , Marechal Marion Le , Pondérand Léa , Mounayar Anne Laure , Lejeune Sophie , Arata-Bardet Julie , Gallouche Meghann , Recule Christine , Maubon Danièle , Garnaud Cécile , Cornet Muriel , Veloso Mélanie , Chabani Bilel , Maurin Max , David-Tchouda Sandra , Pavese Patricia
Published: February 2024

Purpose. To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI).
Methods. Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12h after transmission of positivity and Gram stain results from the first positive BC.
Results. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, IC95% [77.5 ; 91.8] vs. 68/107 = 63.6%, IC95% [53.7 ; 72.6]; p<10-3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9h, IQR [2.9; 17.8] vs 26.4h, IQR [3.4; 47.5]; p=0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4% to 8.8% (p=0.306), with a tendency for a lower median length of stay (18 vs. 20 days; p=0.064) and a non-significant reduction in the average cost per patient of €3,065 (p=0.15). mPCR identified all the bacteria present in 88% of the samples.
Conclusion. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.
A mathematical-computational model explains phenotypic plasticity changes by mutations underlying hepatic cancer stem cells emergence
Authors: Álvarez-Buylla Elena R. , Hernández-Magaña Alexis , Bensussen Antonio , Martinez-Garcia Juan Carlos
Published: February 2024

In several carcinomas, including hepatocellular carcinoma, it has been demonstrated that cancer stem cells (CSCs) have enhanced invasiveness and therapy resistance compared to differentiated cancer cells. Mathematical-computational tools could be valuable for integrating experimental results and understanding the phenotypic plasticity mechanisms for CSCs emergence. Based on the literature review, we constructed a Boolean model that recovers eight stable states (attractors) corresponding to the gene expression profile of hepatocytes and mesenchymal cells in senescent, quiescent, proliferative, and stem-like states. The epigenetic landscape associated with the regulatory network was analyzed. We observed that the loss of p53, p16, RB, or the constitutive activation of β-catenin and YAP1 increases the robustness of the proliferative stem-like phenotypes. Additionally, we found that p53 inactivation facilitates the transition of proliferative hepatocytes into stem-like mesenchymal phenotype. Thus, phenotypic plasticity may be altered, and stem-like phenotypes related to CSCs may be easier to attain following the mutation acquisition.