bluuebunny/crossref_metadata_2025 huggingface dataset:
Associated factors with voriconazole plasma concentration: a systematic review and meta-analysis
Authors: Li Xiaoqi , Hu Qiaozhi , Xu Ting
Published: August 2024

Background: Voriconazole plasma concentration exhibits significant variability and maintaining it within the therapeutic range is the key to enhancing its efficacy. We conducted a systematic review and meta-analysis to estimate the prevalence of patients achieving the therapeutic range of plasma voriconazole concentration and identify associated factors.

Methods: Eligible studies were identified through the PubMed, Embase, Cochrane Library, and Web of Science databases from their inception until 18 November 2023. We conducted a meta-analysis using a random-effects model to determine the prevalence of patients who reached the therapeutic plasma voriconazole concentration range. Factors associated with plasma voriconazole concentration were summarized from the included studies.

Results: Of the 60 eligible studies, 52 reported the prevalence of patients reaching the therapeutic range, while 20 performed multiple linear regression analyses. The pooled prevalence who achieved the therapeutic range was 56% (95% CI: 50%–63%) in studies without dose adjustment patients. The pooled prevalence of adult patients was 61% (95% CI: 56%–65%), and the pooled prevalence of children patients was 55% (95% CI: 50%–60%) The study identified, in the children population, several factors associated with plasma voriconazole concentration, including age (coefficient 0.08, 95% CI: 0.01 to 0.14), albumin (−0.05 95% CI: −0.09 to −0.01), in the adult population, some factors related to voriconazole plasma concentration, including omeprazole (1.37, 95% CI 0.82 to 1.92), pantoprazole (1.11, 95% CI: 0.17–2.04), methylprednisolone (−1.75, 95% CI: −2.21 to −1.30), and dexamethasone (−1.45, 95% CI: −2.07 to −0.83).

Conclusion: The analysis revealed that only approximately half of the patients reached the plasma voriconazole concentration therapeutic range without dose adjustments and the pooled prevalence of adult patients reaching the therapeutic range is higher than that of children. Therapeutic drug monitoring is crucial in the administration of voriconazole, especially in the children population. Particular attention may be paid to age, albumin levels in children, and the use of omeprazole, pantoprazole, dexamethasone and methylprednisolone in adults.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023483728.
Watercress oil loaded with gel: evaluation of hemolysis inhibition, antioxidant, antimicrobial, and healing properties
Authors: Alharbi Bandar , Qanash Husam , Almashjary Majed N. , Barnawi Heba , Aldarhami Abdu , Alsaif Ghaida , Alsamaan Fahad , Monjed Mohammad Khalil , Al Shmrany Humood , Bazaid Abdulrahman S.
Published: August 2024

Plant-derived compounds are renowned for their remarkable pharmacological properties, holding immense promise for therapeutic interventions in human health. In this study, we aimed to assess the antimicrobial, anti-hemolytic, antioxidant, and wound healing attributes of watercress oil incorporated into Vaseline gel (OLG) compared to watercress oil alone. OLG was formulated through a meticulous process involving the addition of Vaseline gel to the oil under agitation conditions. High-performance liquid chromatography analysis of watercress oil unveiled a rich array of phenolic compounds, including gallic acid (10.18 μg/mL), daidzein (3.46 μg/mL), and hesperetin (3.28 μg/mL). The inhibitory zones caused by watercress oil alone against a spectrum of pathogens, including Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Candida albicans, were measured at 25 ± 0.3, 26 ± 0.1, 22 ± 0.2, 25 ± 0.2, and 24 ± 0.1 mm, respectively. Notably, OLG exhibited slightly larger zones of inhibition (27 ± 0.2, 30 ± 0.2, 24 ± 0.1, 28 ± 0.1, and 25 ± 0.3 mm) against the same microbial strains. Furthermore, the minimum inhibitory concentration (MIC) of OLG against E. coli and E. faecalis was lower compared to watercress oil alone, indicating enhanced efficacy. Similarly, the minimum bactericidal concentration (MBC) of OLG was notably lower across all tested bacteria compared to watercress oil alone. Inhibition of bacterial hemolysis, particularly K. pneumoniae, was significantly enhanced with OLG treatment, showcasing reductions of 19.4%, 11.6%, and 6.8% at 25%, 50%, and 75% MIC concentrations, respectively, compared to watercress oil alone. The antioxidant activity of both oil and OLG was quantified with IC50 values of 2.56 and 3.02 μg/mL, respectively. Moreover, OLG demonstrated remarkable efficacy in wound healing assays, with notable enhancements in migration rate, wound closure, and area difference compared to control cells. In light of the observed antibacterial, antifungal, anti-hemolytic, and wound healing properties of OLG, this formulation holds therapeutic potential in treating microbial infections and promoting wound healing.
Design and evaluation of magnetic-targeted bilosomal gel for rheumatoid arthritis: flurbiprofen delivery using superparamagnetic iron oxide nanoparticles
Authors: Mushtaq Rayan Y. , Naveen Nimbagal Raghavendra , Rolla Krishna Jayanth , Al Shmrany Humood , Alshehri Sameer , Salawi Ahmad , Kurakula Mallesh , Alghamdi Majed A. , Rizg Waleed Y. , Bakhaidar Rana B. , Abualsunun Walaa A. , Hosny Khaled M. , Alamoudi Abdulmohsin J.
Published: August 2024

Introduction

The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities.

Methods

The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel.

Results

The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel.

Discussion

This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation’s applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation’s efficacy, underscoring its potential for improving the treatment of osteoarthritis.
Nitrate and ammonium, the yin and yang of nitrogen uptake: a time-course transcriptomic study in rice
Authors: Pélissier Pierre-Mathieu , Parizot Boris , Jia Letian , De Knijf Alexa , Goossens Vera , Gantet Pascal , Champion Antony , Audenaert Dominique , Xuan Wei , Beeckman Tom , Motte Hans
Published: August 2024

Nitrogen is an essential nutrient for plants and a major determinant of plant growth and crop yield. Plants acquire nitrogen mainly in the form of nitrate and ammonium. Both nitrogen sources affect plant responses and signaling pathways in a different way, but these signaling pathways interact, complicating the study of nitrogen responses. Extensive transcriptome analyses and the construction of gene regulatory networks, mainly in response to nitrate, have significantly advanced our understanding of nitrogen signaling and responses in model plants and crops. In this study, we aimed to generate a more comprehensive gene regulatory network for the major crop, rice, by incorporating the interactions between ammonium and nitrate. To achieve this, we assessed transcriptome changes in rice roots and shoots over an extensive time course under single or combined applications of the two nitrogen sources. This dataset enabled us to construct a holistic co-expression network and identify potential key regulators of nitrogen responses. Next to known transcription factors, we identified multiple new candidates, including the transcription factors OsRLI and OsEIL1, which we demonstrated to induce the primary nitrate-responsive genes OsNRT1.1b and OsNIR1. Our network thus serves as a valuable resource to obtain novel insights in nitrogen signaling.
Arabidopsis TIC236 contributes to proplastid development and chloroplast biogenesis during embryogenesis
Authors: Liu Mei , Chen Lifen , Gu Shijie , Zhang Aiwei , Tong Mengjuan , Wang Shuailei , Wang Juntao , Zhu Yirui , Zhang Jingsheng , Sun Yu , Guo Yi , Li Rui
Published: August 2024

Plastids are essential, semi-autonomous organelles in plants that carry out a multitude of functions during development. Plastids existing in different subtypes are derived from proplastids progenitors and interconvert in response to environmental and growth cues. Most efforts focus on the differentiation from proplastid to other forms. However, the studies of proplastid development are insufficient and whether proplastid biogenesis affects plant growth is yet to be determined. Arabidopsis TIC236, a translocon component at the inner membrane of the chloroplast envelope, is critical for importing chloroplast-targeted preproteins and chloroplast division. In this study, we uncovered the fundamental influence of proplastid biogenesis on embryo development by exploring the function of TIC236 during embryogenesis. Widespread and strong expression of TIC236 was observed in leaves and embryos. The null mutant tic236 had an embryo-lethal phenotype, with cell division in the mutant embryos delayed starting at the octant stage and arrested at the globular stage. Transmission electron microscopy revealed enlarged proplastids with an aberrant inner structure at the dermatogen and globular stages that ultimately did not differentiate into chloroplasts. Additionally, the fluorescence signal distribution patterns of tic236 embryos carrying the pDR5rev::3xVENUS-N7, pPIN1::PIN1-GFP, pWOX5::GFP, and pSCR::H2B-YFP reporter systems were altered. Together, we provide genetic evidence supporting proplastid biogenesis plays a vital role in embryo development and TIC236 is identified as an indispensable player, ensuring normal proplastid development.
Factor structure and measurement invariance of the University Demand-Resource Questionnaire: further evidence from Hungarian university students
Authors: Sun Guo-Dong , Chen Hua-Ke , Sun Wei-Xing , Szabó Éva , Tóth Enikő , Hu Jin-Chuan , Jagodics Balázs , Liu Jing-Dong
Published: August 2024

Purpose

The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students.

Methods

Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples.

Results

It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach’s alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples.

Conclusion

The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students.
Combined impact of elevated C-reactive protein levels and dyslipidemia on stroke: a CHNS prospective cohort study
Authors: Lv Meiru , Su Chang , Huang Feifei , Jia Xiaofang , Zhang Jiguo , Wang Huijun , Wu Xiaoyu , Zhou Weiwei , Du Wenwen
Published: August 2024

Background

The objective of this study was to examine whether the combination of elevated levels of C-reactive protein (CRP) and dyslipidemia increased the risk of stroke among middle-aged and older adult individuals in China.

Methods

This study utilized longitudinal data from the China Health and Nutrition Survey (CHNS) collected in 2009, 2015, and 2018. A total of 8,023 participants aged ≥40 years (3,595 males and 4,428 females) were included. The Generalized Estimating Equation (GEE) method was employed to examine the association between inflammation, dyslipidemia, their combined effects, and stroke in the Chinese population.

Results

A total of 174 stroke events occurred during follow-up. Compared with those with normal CRP levels (CRP ≤ 3 mg/L), the adjusted ORs and 95%CI were 2.13 (1.25, 3.64) for the female with elevated CRP level. Compared with those with non-dyslipidemia, the adjusted ORs and 95%CI were 1.56 (1.03, 2.37) for the individuals with high LDL cholesterol, 1.93 (1.12, 3.33) for the male with high LDL cholesterol. Compared with those with normal CRP levels and non-dyslipidemia, the adjusted ORs and 95%CI were 1.74 (1.08, 2.78) for the individuals with elevated CRP levels and dyslipidemia, 2.41 (1.29, 4.49) for the male with elevated CRP levels and dyslipidemia. People with the coexistence of elevated CRP levels and dyslipidemia had the highest risk of stroke among male.

Conclusion

In females, higher levels of inflammation are associated with an increased incidence of stroke. In males, individuals with dyslipidemia characterized by high LDL cholesterol levels are more susceptible to stroke. In the general population, the joint effect of inflammation and dyslipidemia predisposes individuals to a higher risk of stroke, particularly among males.
Normothermic Regional Perfusion in Controlled Donation After Circulatory Death Liver Transplantation: A Systematic Review and Meta-Analysis
Authors: Mastrovangelis Carly , Frost Charles , Hort Amy , Laurence Jerome , Pang Tony , Pleass Henry
Published: August 2024

Liver grafts from controlled donation after circulatory death (cDCD) donors have lower utilization rates due to inferior graft and patient survival rates, largely attributable to the increased incidence of ischemic cholangiopathy, when compared with grafts from brain dead donors (DBD). Normothermic regional perfusion (NRP) may improve the quality of cDCD livers to allow for expansion of the donor pool, helping to alleviate the shortage of transplantable grafts. A systematic review and metanalysis was conducted comparing NRP cDCD livers with both non-NRP cDCD livers and DBD livers. In comparison to non-NRP cDCD outcomes, NRP cDCD grafts had lower rates of ischemic cholangiopathy [RR = 0.23, 95% CI (0.11, 0.49), p = 0.0002], primary non-function [RR = 0.51, 95% CI (0.27, 0.97), p = 0.04], and recipient death [HR = 0.5, 95% CI (0.36, 0.69), p < 0.0001]. There was no difference in outcomes between NRP cDCD donation compared to DBD liver donation. In conclusion, NRP improved the quality of cDCD livers compared to their non-NRP counterparts. NRP cDCD livers had similar outcomes to DBD grafts. This provides further evidence supporting the continued use of NRP in cDCD liver transplantation and offers weight to proposals for its more widespread adoption.
Ideogramy w piśmie japońskim oraz w piśmie polskim z punktu widzenia semiotyki – o pewnej analogii grafemicznej obu języków
Authors: Waśniewski Grzegorz P.
Published: August 2024

Within the graphemic system, Polish, like many other languages using the Latin alphabet, displays a certain characteristic analogy with the ideographic Sino-Japanese script used in the Japanese language. The analogy involves the presence of a small set of digital ideograms used to write numerical expressions. These expressions, contrary to digital rows representing mathematical formulae, are elements of the natural language lexicon, and their digital notation is abbreviated following the principle of linguistic economy. This principle prompts users to annotate digital ideograms with alphabetical markers that cue their pronunciation in the text.
Analgesic Effect of Dexmedetomidine-Nalbuphine Combination vs. Dexmedetomidine Alone in Donkeys Undergoing Field Castration under Total Intravenous Anesthesia
Authors: Helal Ibrahim E. , Al-Abbadi Hatim A. , Hashem Mohamed A. , Abdelrazek Heba M. A. , Shekidef Mohammed H. , Ahmed Mahmoud F.
Published: August 2024

This study evaluated the antinociceptive effect of dexmedetomidine-nalbuphine vs. dexmedetomidine alone in jacks undergoing field castration under total intravenous anesthesia. Jacks were premedicated with intravenous (IV) dexmedetomidine (5 µg/kg), either alone (Group D, n = 6) or in combination with 0.3 mg/kg nalbuphine (Group DN, n = 6). IV ketamine (1.5 mg/kg) and propofol (0.5 mg/kg) were used to induce general anesthesia, which was maintained by a continuous propofol (0.2 mg/kg/min) IV infusion. The quality of anesthesia, analgesia, and recovery were evaluated. A simple descriptive scale (SDS) was used to measure pain from the recovery time to 6 h later. The DN group exhibited improvements in analgesic and recovery quality and SDS of pain at 1-, 2-, and 3-h post-recovery. There was an apparent improvement in cardiac status, as evidenced by the enhanced heart rate and electrocardiogram findings compared to group D during surgery and recovery time. The DN group had a lower level of inflammatory cytokines, both during the surgery and shortly after recovery. Therefore, the dexmedetomidine-nalbuphine combination prior to IV anesthesia of ketamine and propofol in jacks undergoing field castration resulted in a stable surgical plane of anesthesia, improved antinociception, less pain postoperatively, and better cardiac stability.
Determining the Optimal Harvesting Moment of Green Forage from Guizotia abyssinica Cultivated as a Catch Crop on Silage and Its Quality Form, Fresh or Wilted Green Material, in the Two Following Years
Authors: Szuba-Trznadel Anna , Hikawczuk Tomasz , Jama-Rodzeńska Anna , Kamińska Joanna , Svecnjak Zlatko , Król Zygmunt , Fuchs Bogusław
Published: August 2024

Guizotia abyssinica is currently being used for soil improvement; however, owing to its rapid growth and high productivity, it may have value as feed for ruminants, although this has not been well studied. Thus, this research aimed to evaluate the silage quality of Guizotia abyssinica grown during the short season (July–October) as a catch crop in northern Europe when harvested 58, 68, and 90 days after sowing (DAS) over two production years. Ensiled material was analyzed to compare silage quality for the three different DAS. Two factors were analyzed factorially in the experiment: the silage preparation year (2018 or 2019) and the form of the ensiled material (fresh or wilted). We used 36 replications, 18 for each variant of the experimental factor. Harvesting at 58 DAS resulted in unsatisfactory forage fermentability, even after wilting. At 68 DAS, silage quality was satisfactory, but the dry matter content before ensiling was below 20% for both fresh and wilted forage, indicating limitations for silage use without additional wilting for that DAS harvest time. Dry matter content and water-soluble carbohydrates consistently increased as harvest was delayed. Thus, the highest silage quality was obtained from forage harvested 90 DAS regardless of differences in dry matter content. Therefore, it is possible to prepare silage at lower temperatures when the wilting process is limited by environmental conditions.
Constructing British Selfhood through Depictions of China: The Art of the Macartney Embassy
Authors: Chen Yushu , Huang Bing
Published: August 2024

The Macartney Embassy, the first official British diplomatic mission to China, contributed to the visual record and understanding of China in Britain. The embassy artists were ambitious in their mission to deliver authentic visual knowledge of China to the British at the same time that they were subconsciously influenced by both the old chinoiserie tradition, and the nascent British Enlightenment thought process. In contrast to contemporary Britain’s scientific and humanitarian advancements, the embassy’s portrayal of China was pastoral, barbaric, and autocratic, allowing the British to revel in the humanism and progressivism of their own values and social system.
Chronobiology of Cancers in the Liver and Gut
Authors: Ferrell Jessica M.
Published: August 2024

Circadian rhythms dictate the timing of cellular and organismal physiology to maintain homeostasis. Within the liver and gut, circadian rhythms influence lipid and glucose homeostasis, xenobiotic metabolism, and nutrient absorption. Disruption of this orchestrated timing is known to negatively impact human health and contribute to disease progression, including carcinogenesis. Dysfunctional core clock timing has been identified in malignant growths and may be used as a molecular signature of disease progression. Likewise, the circadian clock and its downstream effectors also represent potential for novel therapeutic targets. Here, the role of circadian rhythms in the pathogenesis of cancers of the liver and gut will be reviewed, and chronotherapy and chronopharmacology will be explored as potential treatment options.
How to Tackle Discordance in Adjuvant Chemotherapy Recommendations by Using Oncotype DX Results, in Early-Stage Breast Cancer
Authors: Boér Katalin , Kaposi Ambrus , Kocsis Judit , Horváth Zsolt , Madaras Balázs , Sávolt Ákos , Klément Gyorgy Benjamin , Rubovszky Gábor
Published: August 2024

Background: The use of the Oncotype DX test reduces the rate of adjuvant chemotherapy recommendations. Few in-depth analyses have been performed on this decision-making process. Methods: We retrospectively analyzed patient data based on available Oncotype DX test results (RS) irrespective of nodal status at a single center. We collected recommendations from six oncologists, first without RS (pre-RS) and then with RS results (post-RS). We investigated changes in recommendations, agreement between oncologist decisions, and the effect of different National Comprehensive Cancer Network (NCCN) recommendation categories (for, against, and considering chemotherapy). Results: Data from 201 patients were included in the analysis. Recommendation of chemotherapy decreased by an average of 39.5%. Agreement improved substantially with RS, with a kappa value pre-RS of 0.37 (fair agreement) and post-RS of 0.75 (substantial agreement). Discordance remained substantial in cases where the NCCN recommendations considered chemotherapy only (32%). Pre-RS consensus against chemotherapy predicted low RS results (50 out of 51 patients). Post-RS consensus was highest in the NCCN chemotherapy recommendation group. Conclusions: The Oncotype DX test substantially improves decision accuracy in recommending adjuvant chemotherapy. It may be further improved with a consensus decision. In the case of pre-RS consensus against chemotherapy, the test can be spared.
Updates on Therapeutic Strategies in the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Parekh Deevyashali S. , Tiger Yun Kyoung Ryu , Jamouss Kevin Tony , Hassani Justin , Bou Zerdan Maroun , Raza Shahzad
Published: August 2024

Multiple myeloma is a heterogeneous condition characterized by the proliferation of monoclonal B-cells, for which there is currently no curative treatment available. Relapses are, unfortunately, common after first-line treatment. While the prognosis for relapsed refractory multiple myeloma is generally poor, advances in the treatment of relapsed or refractory multiple myeloma offer hope. However, the expansion of effective options in targeted treatment offers renewed optimism and hope that patients who fail on older therapies may respond to newer modalities, which are often used in combination. We review currently approved and novel investigational agents classified by mechanisms of action, efficacy, approved setting, and adverse events. We delve into future directions of treatment for relapsed/refractory multiple myeloma, reviewing novel agents and therapeutic targets for the future.
Vitamin D3 Upregulated Protein 1 Deficiency Promotes Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Carcinogenesis in Mice
Authors: Park Ki Hwan , Kim Hyoung-Chin , Won Young-Suk , Yoon Won Kee , Choi Inpyo , Han Sang-Bae , Kang Jong Soon
Published: August 2024

VDUP1 acts as a tumor suppressor gene in various cancers. VDUP1 is expressed at low levels in sporadic and ulcerative-colitis-associated colorectal cancer. However, the effects of VDUP1 deficiency on CAC remain unclear. In this study, we found that VDUP1 deficiency promoted CAC development in mice. Wild-type (WT) and VDUP1 KO mice were used to investigate the role of VDUP1 in the development of azoxymethane (AOM)- and dextran sulfate sodium (DSS)-induced CAC. VDUP1 levels significantly decreased in the colonic tumor and adjacent nontumoral tissues of WT mice after AOM/DSS treatment. Moreover, AOM/DSS-treated VDUP1 KO mice exhibited a worse survival rate, disease activity index, and tumor burden than WT mice. VDUP1 deficiency significantly induced cell proliferation and anti-apoptosis in tumor tissues of VDUP1 KO mice compared to WT littermates. Additionally, mRNA levels of interleukin-6 and tumor necrosis factor-alpha and active forms of signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 were significantly increased in the tumor tissues of VDUP1 KO mice. Overall, this study demonstrated that the loss of VDUP1 promoted AOM/DSS-induced colon tumorigenesis in mice, highlighting the potential of VDUP1-targeting strategies for colon cancer prevention and treatment.
MRI T2w Radiomics-Based Machine Learning Models in Imaging Simulated Biopsy Add Diagnostic Value to PI-RADS in Predicting Prostate Cancer: A Retrospective Diagnostic Study
Authors: Liu Jia-Cheng , Ruan Xiao-Hao , Chun Tsun-Tsun , Yao Chi , Huang Da , Wong Hoi-Lung , Lai Chun-Ting , Tsang Chiu-Fung , Ho Sze-Ho , Ng Tsui-Lin , Xu Dan-Feng , Na Rong
Published: August 2024

Background: Currently, prostate cancer (PCa) prebiopsy medical image diagnosis mainly relies on mpMRI and PI-RADS scores. However, PI-RADS has its limitations, such as inter- and intra-radiologist variability and the potential for imperceptible features. The primary objective of this study is to evaluate the effectiveness of a machine learning model based on radiomics analysis of MRI T2-weighted (T2w) images for predicting PCa in prebiopsy cases. Method: A retrospective analysis was conducted using 820 lesions (363 cases, 457 controls) from The Cancer Imaging Archive (TCIA) Database for model development and validation. An additional 83 lesions (30 cases, 53 controls) from Hong Kong Queen Mary Hospital were used for independent external validation. The MRI T2w images were preprocessed, and radiomic features were extracted. Feature selection was performed using Cross Validation Least Angle Regression (CV-LARS). Using three different machine learning algorithms, a total of 18 prediction models and 3 shape control models were developed. The performance of the models, including the area under the curve (AUC) and diagnostic values such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were compared to the PI-RADS scoring system for both internal and external validation. Results: All the models showed significant differences compared to the shape control model (all p < 0.001, except SVM model PI-RADS+2 Features p = 0.004, SVM model PI-RADS+3 Features p = 0.002). In internal validation, the best model, based on the LR algorithm, incorporated 3 radiomic features (AUC = 0.838, sensitivity = 76.85%, specificity = 77.36%). In external validation, the LR (3 features) model outperformed PI-RADS in predictive value with AUC 0.870 vs. 0.658, sensitivity 56.67% vs. 46.67%, specificity 92.45% vs. 84.91%, PPV 80.95% vs. 63.64%, and NPV 79.03% vs. 73.77%. Conclusions: The machine learning model based on radiomics analysis of MRI T2w images, along with simulated biopsy, provides additional diagnostic value to the PI-RADS scoring system in predicting PCa.
Real-World Cardiotoxicity in Metastatic Melanoma Patients Treated with Encorafenib and Binimetinib
Authors: Pedersen Sidsel , Nielsen Marc Østergaard , Donia Marco , Svane Inge Marie , Zerahn Bo , Ellebaek Eva
Published: August 2024

Modern therapies targeting the BRAF gene mutation in advanced melanoma have significantly improved patient outcomes but pose cardiovascular risks. This retrospective study in Eastern Denmark (2019–2022) assessed 108 melanoma patients treated with encorafenib and binimetinib. Patients were monitored for heart function using multigated acquisition (MUGA) scans. The study defined major cardiotoxicity as a decline in left ventricular ejection fraction (LVEF) by more than 10 percentage points to below 50%, and minor cardiotoxicity as a decrease in LVEF by more than 15 points but remaining above 50%. Results showed that 19 patients (18%) developed minor cardiotoxicity and were asymptomatic, while 7 (6%) experienced major cardiotoxicity, with two requiring intervention. Notably, no significant declines in LVEF were observed after six months of treatment. The study concluded that significant cardiotoxicity occurred in 6% of cases, mostly asymptomatic and reversible, and suggests that monitoring LVEF could potentially be reduced after 6–9 months if no early signs of cardiotoxicity are detected. This provides valuable insights into the cardiac safety of these treatments in real-world settings.
Escalation and De-Escalation of Adjuvant Radiotherapy in Early Breast Cancer: Strategies for Risk-Adapted Optimization
Authors: Gruber Guenther
Published: August 2024

Postoperative radiotherapy (RT) is recommended after breast-conserving surgery and mastectomy (with risk factors). Consideration of pros and cons, including potential side effects, demands the optimization of adjuvant RT and a risk-adapted approach. There is clear de-escalation in fractionation—hypofractionation should be considered standard. For selected low-risk situations, PBI only or even the omission of RT might be appropriate. In contrast, tendencies toward escalating RT are obvious. Preoperative RT seems attractive for patients in whom breast reconstruction is planned or for defining the tumor location more precisely with the potential of giving ablative doses. Dose escalation by a (simultaneous integrated) boost or the combination with new compounds/systemic treatments may increase antitumor efficacy but also toxicity. Despite low evidence, RT for oligometastatic disease is becoming increasingly popular. The omission of axillary dissection in node-positive disease led to an escalation of regional RT. Studies are ongoing to test if any axillary treatment can be omitted and which oligometastatic patients do really benefit from RT. Besides technical improvements, the incorporation of molecular risk profiles and also the response to neoadjuvant systemic therapy have the potential to optimize the decision-making concerning if and how local and/or regional RT should be administered.
3D-Bioprinted Co-Cultures of Glioblastoma Multiforme and Mesenchymal Stromal Cells Indicate a Role for Perivascular Niche Cells in Shaping Glioma Chemokine Microenvironment
Authors: Zielniok Katarzyna , Rusinek Kinga , Słysz Anna , Lachota Mieszko , Bączyńska Ewa , Wiewiórska-Krata Natalia , Szpakowska Anna , Ciepielak Martyna , Foroncewicz Bartosz , Mucha Krzysztof , Zagożdżon Radosław , Pojda Zygmunt
Published: August 2024

3D bioprinting has become a valuable tool for studying the biology of solid tumors, including glioblastoma multiforme (GBM). Our analysis of publicly available bulk RNA and single-cell sequencing data has allowed us to define the chemotactic profile of GBM tumors and identify the cell types that secrete particular chemokines in the GBM tumor microenvironment (TME). Our findings indicate that primary GBM tissues express multiple chemokines, whereas spherical monocultures of GBM cells significantly lose this diversity. Subsequently, the comparative analysis of GBM spherical monocultures vs. 3D-bioprinted multicultures of cells showed a restoration of chemokine profile diversity in 3D-bioprinted cultures. Furthermore, single-cell RNA-Seq analysis showed that cells of the perivascular niche (pericytes and endocytes) express multiple chemokines in the GBM TME. Next, we 3D-bioprinted cells from two glioblastoma cell lines, U-251 and DK-MG, alone and as co-cultures with mesenchymal stromal cells (representing cells of the perivascular niche) and assessed the chemokine secretome. The results clearly demonstrated that the interaction of tumors and mesenchymal cells leads to in a significant increase in the repertoire and levels of secreted chemokines under culture in 21% O2 and 1% O2. Our study indicates that cells of the perivascular niche may perform a substantial role in shaping the chemokine microenvironment in GBM tumors.
In Vitro Safety Study on the Use of Cold Atmospheric Plasma in the Upper Respiratory Tract
Authors: Karrer Sigrid , Unger Petra , Gruber Michael , Gebhardt Lisa , Schober Robert , Berneburg Mark , Bosserhoff Anja Katrin , Arndt Stephanie
Published: August 2024

Cold atmospheric plasma (CAP) devices generate reactive oxygen and nitrogen species, have antimicrobial and antiviral properties, but also affect the molecular and cellular mechanisms of eukaryotic cells. The aim of this study is to investigate CAP treatment in the upper respiratory tract (URT) to reduce the incidence of ventilator-associated bacterial pneumonia (especially superinfections with multi-resistant pathogens) or viral infections (e.g., COVID-19). For this purpose, the surface-microdischarge-based plasma intensive care (PIC) device was developed by terraplasma medical GmbH. This study analyzes the safety aspects using in vitro assays and molecular characterization of human oral keratinocytes (hOK), human bronchial–tracheal epithelial cells (hBTE), and human lung fibroblasts (hLF). A 5 min CAP treatment with the PIC device at the “throat” and “subglottis” positions in the URT model did not show any significant differences from the untreated control (ctrl.) and the corresponding pressurized air (PA) treatment in terms of cell morphology, viability, apoptosis, DNA damage, and migration. However, pro-inflammatory cytokines (MCP-1, IL-6, and TNFα) were induced in hBTE and hOK cells and profibrotic molecules (collagen-I, FKBP10, and αSMA) in hLF at the mRNA level. The use of CAP in the oropharynx may make an important contribution to the recovery of intensive care patients. The results indicate that a 5 min CAP treatment in the URT with the PIC device does not cause any cell damage. The extent to which immune cell activation is induced and whether it has long-term effects on the organism need to be carefully examined in follow-up studies in vivo.
Increasing the Security of Network Data Transmission with a Configurable Hardware Firewall Based on Field Programmable Gate Arrays
Authors: Grossi Marco , Alfonsi Fabrizio , Prandini Marco , Gabrielli Alessandro
Published: August 2024

One of the most common mitigations against network-borne security threats is the deployment of firewalls, i.e., systems that can observe traffic and apply rules to let it through if it is benign or drop packets that are recognized as malicious. Cheap and open-source (a feature that is greatly appreciated in the security world) software solutions are available but may be too slow for high-rate channels. Hardware appliances are efficient but opaque and they are often very expensive. In this paper, an open-hardware approach is proposed for the design of a firewall, implemented on off-the-shelf components such as an FPGA (the Xilinx KC705 development board), and it is tested using controlled Ethernet traffic created with a packet generator as well as with real internet traffic. The proposed system can filter packets based on a set of rules that can use the whitelist or blacklist approach. It generates a set of statistics, such as the number of received/transmitted packets and the amount of received/transmitted data, which can be used to detect potential anomalies in the network traffic. The firewall has been experimentally validated in the case of a network data throughput of 1 Gb/s, and preliminary simulations have shown that the system can be upgraded with minor modifications to work at 10 Gb/s. Test results have shown that the proposed firewall features a latency of 627 ns and a maximum data throughput of 0.982 Gb/s.
Association between Complex ACTN3 and ACE Gene Polymorphisms and Elite Endurance Sports in Koreans: A Case–Control Study
Authors: Chae Ji Heon , Eom Seon-Ho , Lee Sang-Ki , Jung Joo-Ha , Kim Chul-Hyun
Published: August 2024

ACTN3 R577X and ACE I/D polymorphisms are associated with endurance exercise ability. This case–control study explored the association of ACTN3 and ACE gene polymorphisms with elite pure endurance in Korean athletes, hypothesizing that individuals with both ACTN3 XX and ACE II genotypes would exhibit superior endurance. We recruited 934 elite athletes (713 males, 221 females) and selected 45 pure endurance athletes (36 males, 9 females) requiring “≥90% aerobic energy metabolism during sports events”, in addition to 679 healthy non-athlete Koreans (361 males, 318 females) as controls. Genomic DNA was extracted and genotyped for ACTN3 R577X and ACE I/D polymorphisms. ACE ID (p = 0.090) and ACTN3 RX+XX (p = 0.029) genotype distributions were significantly different between the two groups. Complex ACTN3-ACE genotypes also exhibited significant differences (p = 0.014), with dominant complex genotypes positively affecting endurance (p = 0.039). The presence of RX+II or XX+II was associated with a 1.763-fold higher likelihood of possessing a superior endurance capacity than that seen in healthy controls (90% CI = 1.037–3.089). Our findings propose an association of combined ACTN3 RX+XX and ACE II genotypes with enhanced endurance performance in elite Korean athletes. While causality remains to be confirmed, our study highlights the potential of ACTN3-ACE polymorphisms in predicting elite endurance.
Addressing Health Illiteracy and Stunting in Culture-Shocked Indigenous Populations: A Case Study of Outer Baduy in Indonesia
Authors: Putri Liza Diniarizky , Agustin Herlina , Bakti Iriana , Suminar Jenny Ratna
Published: August 2024

This research aims to determine the factors, impacts, and solutions for health literacy in the Outer Baduy hamlets of Kanekes Village, Indonesia. The method used in this research is qualitative, which produces an in-depth explanation of the existing problems. Data were collected through interviews and documentation. Interviews were conducted with key figures, including two female Baduy residents with stunted children, one retainer, the head of the NGO SRI, a midwife who works in the Baduy village, and the head of the Lebak social service. Apart from that, secondary data in the form of recordings of community service talk shows conducted by the University of Indonesia to overcome stunting in Baduy were also analysed. The results show that the factors associated with the low health literacy of the Baduy community are literacy, writing and reading, taboos on eating certain foods, people spending too much time in the fields, people learning by imitating their parents, demanding access to villages, lack of consistency from external parties in providing health programs, and gender segregation in Baduy society. The impact of the low health literacy of the Baduy community is fatalism, high maternal and child mortality rates, and high health costs. The proposed strategies for increasing the health literacy of the Baduy community based on the findings of this research include developing health literacy by targeting community leaders, managing information-technology-based health-information groups, and always presenting at least one health worker among the residents who provides an example of healthy living, encouraging collective reflection. when health cases occur, and balancing gender communication.
IKDD: A Keystroke Dynamics Dataset for User Classification
Authors: Tsimperidis Ioannis , Asvesta Olga-Dimitra , Vrochidou Eleni , Papakostas George A.
Published: August 2024

Keystroke dynamics is the field of computer science that exploits data derived from the way users type. It has been used in authentication systems, in the identification of user characteristics for forensic or commercial purposes, and to identify the physical and mental state of users for purposes that serve human–computer interaction. Studies of keystroke dynamics have used datasets created from volunteers recording fixed-text typing or free-text typing. Unfortunately, there are not enough keystroke dynamics datasets available on the Internet, especially from the free-text category, because they contain sensitive and personal information from the volunteers. In this work, a free-text dataset is presented, which consists of 533 logfiles, each of which contains data from 3500 keystrokes, coming from 164 volunteers. Specifically, the software developed to record user typing is described, the demographics of the volunteers who participated are given, the structure of the dataset is analyzed, and the experiments performed on the dataset justify its utility.
Machine Learning and Artificial Intelligence for a Sustainable Tourism: A Case Study on Saudi Arabia
Authors: Louati Ali , Louati Hassen , Alharbi Meshal , Kariri Elham , Khawaji Turki , Almubaddil Yasser , Aldwsary Sultan
Published: August 2024

This work conducts a rigorous examination of the economic influence of tourism in Saudi Arabia, with a particular focus on predicting tourist spending patterns and classifying spending behaviors during the COVID-19 pandemic period and its implications for sustainable development. Utilizing authentic datasets obtained from the Saudi Tourism Authority for the years 2015 to 2021, the research employs a variety of machine learning (ML) algorithms, including Decision Trees, Random Forests, K-Neighbors Classifiers, Gaussian Naive Bayes, and Support Vector Classifiers, all meticulously fine-tuned to optimize model performance. Additionally, the ARIMA model is expertly adjusted to forecast the economic landscape of tourism from 2022 to 2030, providing a robust predictive framework for future trends. The research framework is comprehensive, encompassing diligent data collection and purification, exploratory data analysis (EDA), and extensive calibration of ML algorithms through hyperparameter tuning. This thorough process tailors the predictive models to the unique dynamics of Saudi Arabia’s tourism industry, resulting in robust forecasts and insights. The findings reveal the growth trajectory of the tourism sector, highlighted by nearly 965,073 thousand tourist visits and 7,335,538 thousand overnights, with an aggregate tourist expenditure of SAR 2,246,491 million. These figures, coupled with an average expenditure of SAR 89,443 per trip and SAR 9198 per night, form a solid statistical basis for the employed predictive models. Furthermore, this research expands on how ML and AI innovations contribute to sustainable tourism practices, addressing key aspects such as resource management, economic resilience, and environmental stewardship. By integrating predictive analytics and AI-driven operational efficiencies, the study provides strategic insights for future planning and decision-making, aiming to support stakeholders in developing resilient and sustainable strategies for the tourism sector. This approach not only enhances the capacity for navigating economic complexities in a post-pandemic context, but also reinforces Saudi Arabia’s position as a premier tourism destination, with a strong emphasis on sustainability leading into 2030 and beyond.
Friction and Wear in Hot Stamping: The Role of Tool and Workpiece Temperature and Tool Steel Composition
Authors: Pelcastre Leonardo
Published: August 2024

Hot stamping is a forming process widely used in the manufacturing of structural components in automobiles. It is a versatile process that enables the fabrication of complex-shaped components with high strength. It also facilitates the manufacturing of components that incorporate high-strength sections and high-ductility sections, by controlling the cooling rate. The process is versatile in terms of the microstructures and mechanical properties that can be obtained. This versatility, however, puts high demands on the materials pertaining their stability, wear resistance, costs, etc. This study has focused on understanding the effect of temperature on the tribological response of different tool materials when these are exposed to high temperatures. The results show that friction significantly stabilises with increased temperature for most tool steels. One tool steel behaves more unstably at high temperature, and this is attributed to the presence of Cr7C3, MoO3, and VO and severe wear on the workpiece material. The most severe wear on the workpiece is caused by a partially melted interdiffusion layer, which facilitates the detachment of the Al-Si coating and subsequent transfer onto the tool; this effect is maximised at the highest temperatures of the workpiece. An important finding is that friction and material transfer severity decrease as the workpiece temperature decreases, and friction is stabilised as tool temperature increases without minimising wear or the average friction coefficient.
Dynamic Coefficient Investigation for Supercritical Carbon Dioxide Dry Gas Seal Based on Complete Variable Perturbation Model
Authors: Yan Ruqi , Chai Baodui , Ma Lu , Chen Hanqing , Ding Xuexing
Published: August 2024

In this work, a new model to analyse the dynamic characteristic coefficient of the S-CO2 dry gas seal was reported. Taking into account that the flow within the S-CO2 dry gas seal is close to adiabatic flow, the impact of the temperature change on the dynamic characteristic coefficient of the gas film cannot be ignored. To address this issue, a complete variable perturbation model (CVPM) under the adiabatic flow process was established using the frequency perturbation method while considering multiple complex effects. Then, the finite difference method was used to solve the CVPM. The gas film’s dynamic stiffness and damping coefficients were calculated and analysed for different conditions, operating parameters, and frequency ratios. From our analysis, it was demonstrated that the dynamic coefficient of the gas film exhibited frequency dependence. The turbulence coefficient perturbation had the most remarkable influence on the gas film’s dynamic coefficient, compared to the temperature, viscosity, and centrifugal inertia force perturbations. The isothermal flow, adiabatic flow, inlet pressure, and inlet temperature also affected the magnitude of the dynamic characteristic coefficient of the gas film. However, no significant impact on their tendency to vary with the frequency ratio was found. Our work provides new theoretical support for the dynamic analysis of S-CO2 dry gas seals, which is of great importance for future applications.