bluuebunny/crossref_metadata_2025 huggingface dataset:
Green Finance and Value Realization of Forest Ecological Products in Karst Areas: A Mediating-Effect Perspective Based on the Level of Karst Desertification
Authors: Huang Huiqiong , Xiong Kangning , Li Yongyao , Wang Qi , Yan Jiawang
Published: December 2024

With their unique karst geomorphology and rich biodiversity, forest ecosystems present huge ecological potential, and their ecological products promise great economic value. In this context, an important way to realize the sustainable development of karst areas is the transformation of such ecological potential into economic advantages. In this paper, Guizhou Province, China, one of the most representative regions with karst geomorphology, is examined in a case study. Using the equivalent factor method, the values of forest ecological products in various states of Guizhou Province were calculated for the years 2010, 2015, and 2020. Furthermore, a two-way fixed-effects model was employed to examine the influence of green finance on the realization of these values in the karst region. The findings of this paper are as follows: (1) The value of forest ecological products presented an increasing trend from 2010 to 2020, and green finance significantly promoted the value realization of forest ecological products. Robust estimates could still be obtained after endogeneity control. (2) The results of heterogeneity testing indicated that in karst regions with slower economic development and poor ecological environment, green finance promoted the value realization of forest ecological products more significantly. (3) The mechanism test showed that by providing financial support for rocky desertification control and forest restoration projects, green finance promoted ecological restoration, governance, and vegetation restoration while mitigating rocky desertification; in this way, green finance drove the development of ecological forestry and industrial upgrading to accelerate the value realization of ecological products, thereby strongly supporting the sustainable development of karst areas.
The Safety of Probiotics Intended for Use in Pregnant and Lactating Women: From a Desirable to a Required Task
Authors: Fernández Leónides , Orgaz Belén , Rodríguez Juan M.
Published: December 2024

During pregnancy, women undergo changes that affect virtually every organ, apparatus, or system, including the host microbiota. Most pregnancies progress smoothly despite the common presence of minor side-effects arising from such adaptations. However, some women may experience more serious complications, including gestational diabetes mellitus, preeclampsia, or preterm delivery. Probiotics are one of the products most used to try to prevent or treat any of the minor or severe symptoms or complications that women may experience during pregnancy or lactation; however, most of them have never been tested in such populations and, therefore, their efficacy and safety claims are frequently unsubstantiated. Overall, probiotic trials involving pregnant or lactating women have shown that these products are usually well-tolerated and safe although adverse effects may also exist. Therefore, health professionals attending pregnant or lactating women should be aware of their use and monitor their efficacy and safety. In conclusion, probiotics recommendations for pregnant or lactating women should be based on scientific evidence, opting exclusively for those products that have been designed for the specific target or condition that a pregnant or lactating woman may be experiencing or at risk of, and which efficacy and safety has already been convincingly tested in such populations.
Box-Counting Dimension Sequences of Level Sets in AI-Generated Fractals
Authors: Lee Minhyeok , Lee Soyeon
Published: December 2024

We introduce a mathematical framework to characterize the hierarchical complexity of AI-generated fractals within the finite resolution constraints of digital images. Our method analyzes images produced by text-to-image models at multiple intensity thresholds, employing a discrete level set approach and box-counting dimension estimates. By conducting experiments on fractals created with the FLUX model at a resolution of 128×128, we identify a fully monotonic behavior in the dimension sequences for various box sizes, with inter-scale correlations surpassing 0.95. Pattern-specific dimensional gradients quantify how fractal complexity changes with threshold levels, offering insights into how text-to-image models encode fractal-like geometry through dimensional sequences.
Case Study on the Evaluation of Rock Cut Stability for Highways in Egypt: Implications for Transportation Infrastructure and Safety
Authors: Abdellah Wael R. , Butt Stephen D. , Towfeek Ahmed Rushdy , Hassan Abd El-Samea W. , Abozaied Mahmoud M. , Ali Faisal A. , Ali Mahrous A. M. , Bamousa Abdullah Omar M.
Published: December 2024

This study addresses critical stability concerns along a key segment of the Egyptian highway linking Aswan and Cairo, focusing on a one-kilometer rock-cut section that is vital for transportation and commerce. Recent evaluations have highlighted significant rockfall and slope instability risks in this area, posing serious safety challenges. The primary objective is to identify and analyze the factors contributing to slope instability, assess potential rockfall hazards, and recommend effective mitigation strategies. To achieve this, this study employs a comprehensive, multi-faceted methodology. Key variables influencing slope stability are first identified, followed by a detailed analysis of discontinuity data using stereographic projection based on joint surveys. Rockfall propagation distances are then modeled through specialized software, while the Plaxis 2D tool 2023.2(V23.2.0.1059) is applied for advanced numerical modeling of slope behavior. The results indicate a pressing need for mitigation measures to address ongoing instability issues, including planar and wedge failures and raveling rockfalls, which pose considerable safety risks to road users. This study highlights the necessity of a robust and comprehensive mitigation strategy to ensure road safety and support uninterrupted commercial activity along this essential highway.
From Geohistory to the Future: A Tribute to the Youthful Palaeontological Studies at Gravina in Puglia of Arcangelo Scacchi (1810–1893), the First Modern Geoscientist in the MurGEopark (aUGGp, Southern Italy)
Authors: Lippolis Elio , De Ceglie Rossella , Francescangeli Ruggero , La Perna Rafael , Sabato Luisa , Tropeano Marcello
Published: December 2024

Arcangelo Scacchi (1810–1893) one of the greatest Italian geoscientists known worldwide, especially for his contributions in the fields of mineralogy and volcanology, dedicated his early years to malacological and zoological works. This paper aims to pay homage to a lesser-known side of the scientist, focusing on a malacological work related to fossils from his hometown, Gravina, in Puglia (southern Italy), located within the boundaries of the MurGEopark, which is aspiring to become a UNESCO Global Geopark (aUGGp), and at the border of Parco Nazionale dell’Alta Murgia (Alta Murgia National Park). Among others, Arcangelo Scacchi described 16 new species of molluscs but his precious collection, hosted in Naples, in the Real Museo Mineralogico (Royal Mineralogical Museum), now Museo di Paleontologia dell’Università di Napoli Federico II (Museum of Palaeontology of the University of Naples Federico II), was partly lost. In recent years, research has allowed the resampling of some species he described for the first time in 1835. Starting from this material, the figure of Scacchi was highlighted to the public through the temporal exhibitions and the use of 3D digital models of these resampled fossils. This activity represents: (i) a tribute to the first modern geoscientist who worked in the area of the MurGEopark, (ii) an instrument to preserve palaeontological remains of international importance, and (iii) a public opportunity to know this kind of geocultural heritage enriching the potential examples of (geo)dissemination in the MurGEopark.
Epidemiology of Macrosomia in Saudi Arabia: An Analysis of 12,045 Pregnancies from the Riyadh Mother and Baby Multicenter Cohort Study (RAHMA) Database
Authors: Wahabi Hayfaa , Fayed Amel , Aleyeidi Nouran , Esmaeil Samia
Published: December 2024

Objective: To investigate the prevalence, risk factors, and complications associated with delivering macrosomic babies. Methods: Singleton term pregnancies (12,045) were studied. Macrosomia was categorized using the following two definitions: birthweight > 4 kg and birthweight ≥ 90th percentile (3.7 kg). Regression models were developed to identify significant risk factors for macrosomia such as maternal age, parity, pre-pregnancy body mass index, gestational weight gain, and hyperglycemia. Other models were constructed to identify the independent effect of macrosomia on outcomes such as shoulder dystocia, emergency cesarean section, stillbirth, and low APGAR scores. Results: The 50th centile birth weight of Saudi term infants is 3.18 kg; the 90th and 95th centiles were 3.70 and 3.91 kg, respectively. The prevalence of macrosomia (>4 kg) was 3.4%. The likelihood of macrosomia was associated with maternal age >40 years for newborns >4 kg, OR = 1.88, 95% CI (1.02–3.48), and maternal age < 18 for newborns ≥90th centile, OR = 5.23, 95% CI, (1.05–26.06). Regardless of the classification of macrosomia, it was associated with gestational age ≥41 weeks, parity > 4, pre-pregnancy BMI > 30, and maternal hyperglycemia. Macrosomia, using either definition, was associated with increased risk of shoulder dystocia, OR = 11.45, 95% CI (4.12–31.82) and OR = 9.65, 95% CI (3.89–23.94), and emergency CS, OR = 2.03, 95% CI (1.36–3.08) and OR = 1.77, 95% CI (1.34–1.52), for birthweight > 4 kg and ≥90th centile, respectively. Furthermore, newborns whose weights >4 kg were at greater risk to be stillborn, OR = 4.24, 95% CI (1.18–15.20), and to have low APGAR scores at birth, OR = 3.69, 95% CI (1.25–10.98). Conclusion: The risk of macrosomia among Saudi women significantly increases with maternal age, parity, gestational age, hyperglycemia, and pre-pregnancy obesity. Regardless of the definition used, delivering a macrosomic baby was associated with risks of shoulder dystocia and emergency cesarean section. Newborns (>4 kg) were at greater risk of stillbirth and low APGAR scores.
Frequency of Osteoporosis-Related Fractures in the Kingdom of Bahrain
Authors: Hassan Adla B. , Almarabheh Amer , Almekhyal Abdulaziz , Karashi Ali Redha , Saleh Jamal , Shaikh Mansoor , Alawadhi Abdulhameed , Jahrami Haitham
Published: December 2024

Background: Osteoporosis-related fragility fractures are increasing worldwide. An assessment of the prevalence of fragility fractures in Bahrain is needed to determine proper action and preventive strategies. The main objective of this study was to conduct a retrospective cross-sectional study to investigate the prevalence of fragility fractures in adult Bahraini patients. Another objective was to explore the relationship of fragility fracture risk with BMD, age, sex, BMI, vitamin D status, and therapy. Methods: To investigate the fragility fractures, we retrospectively reviewed the dual-energy X-ray absorptiometry (DEXA) data of patients who underwent scans for the diagnosis of osteoporosis between 2016 and 2018. The data were collected from four large centers in Bahrain. The patients’ medical records were reviewed for the fragility fracture data, BMD, sex, age, BMI, vitamin D status, and therapy. Results: Among a total of 4572 patients who visited the radiology departments during the 3-year study period, only 412 patients with fragility fractures were considered for the current study. The mean age of the patients in this cohort was 63.9 ± 12.2 years. There were 393 females (95.6%). Among the 431 fragility fractures, there were 175 (40.6%) belonging to three common fracture sites: vertebral (86, 20.9%), femur (60, 14.6%), and distal radius (Colles) fractures (29, 7%). Other fragility fractures were hand (7%), radius and ulna (3.7%), humerus (6.5%), tibia and fibula (5.6%), foot/ankle (27.9%), ribs (3.0%), and pelvis (1.6%). Our results revealed a significant association between the fragility fractures and BMD (χ2 = 6.7, p = 0.035). We reported a significant association of fragility fracture with sex (p = 0.006) and with denosumab therapy (p < 0.001). Conclusions: This study reported a reduced BMD and an increased prevalence of fragility fractures among Bahraini subjects. The highest frequencies of fragility fractures among our cohort were foot/ankle, vertebral, and hip fractures, respectively. We showed a statistically significant association between fragility fractures and BMD. The current study indicated that not only patients with low BMD but also patients with fragility fractures were undertreated. Thus, the immediate initiation of treatment and the synthesis of local osteoporosis treatment guidelines are warranted.
Antibiofilm Activity of Epinecidin-1 and Its Variants Against Drug-Resistant Candida krusei and Candida tropicalis Isolates from Vaginal Candidiasis Patients
Authors: Jeyarajan Sivakumar , Ranjith Sukumar , Veerapandian Raja , Natarajaseenivasan Kalimuthusamy , Chidambaram Prahalathan , Kumarasamy Anbarasu
Published: December 2024

Background/Objective: Indwelling intrauterine contraceptive devices (IUDs) have surfaces that facilitate the attachment of Candida spp., creating a suitable environment for biofilm formation. Due to this, vulvovaginal candidiasis (VVC) is frequently linked to IUD usage, necessitating the prompt removal of these devices for effective treatment. In this study, we evaluated the susceptibility of antimicrobial peptides in vitro against biofilm forming, Amphotericin B (MIC50 > 2 mg L−1) resistant Candida krusei and Candida tropicalis isolated from IUD users who had signs of vaginal candidiasis (hemorrhage, pelvic pain, inflammation, itching, and vaginal discharge). Three antimicrobial peptides, namely, epinecidin-1 (epi-1) and its two variants, namely, variant-1 (Var-1) and variant-2 (Var-2), which were reported to have enhanced antibacterial activity were tested against IUD isolates (C. krusei and C. tropicalis) with pathogenic form of Candida albicans as control. Variants of epi-1, namely, Var-1 and Var-2 were created by substituting lysine in the place of histidine and alanine. Methods: The antimicrobial activity was measured using the microbroth dilution method to determine the minimum inhibitory concentration (MIC) of peptides against C. albicans, C. krusei and C. tropicalis. The MIC of each peptide was used for biofilm assay by Crystal violet staining, Scanning Electron Microscopy, and Reactive Oxygen Species (ROS) assay. To find the possible mechanism of anti-biofilm activity by the peptides, their ability to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2 were determined through PatchDock. Results: The MIC values of peptides: epi-1, var-1 and var-2 against C. albicans are 128 μg mL−1, 64 μg mL−1 and 32 μg mL−1, C. tropicalis are 256 μg mL−1, 64 μg mL−1, and 32 μg mL−1 and C. krusei are 128 µg mL−1, 128 µg mL−1 and 64 µg mL−1, respectively. Both the variants outperformed epi-1. Specifically for tested Candida spp., var-1 showed two- to four-fold enhancements and var-2 showed two- to eight-fold enhancements compared to epi-1. Electron microscopy confirmed that the mechanism of action involves pore formation thus inducing reactive oxygen species in Candida spp. cell membrane. Computational analysis showed that the peptides have a high tendency to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2, thereby preventing biofilm formation. Conclusions: The in vitro evidence supports the potential use of epi-1 and its variants to be used as an anti-biofilm agent to coat IUDs in the future for therapeutic purposes.
Precision Oncology Approach for Urachal Carcinoma: A Clinical Case Report
Authors: Juhász Dániel , Csizmarik Anita , Szalontai János , Keszthelyi Attila , Dér Bálint , Kubik András , Szűcs Miklós , Kenessey István , Ertl Iris E. , Berger Walter , Englinger Bernhard , Shariat Shahrokh F. , Nyirády Péter , Szarvas Tibor
Published: December 2024

Urachal cancer (UrC) is a rare disease which is mostly diagnosed late due to symptoms caused by its local invasion to the urinary bladder. Given the lack of clinical trials and guideline recommendations for systemic treatment, a molecularly informed precision oncology approach is a viable option for UrC already in the early lines of systemic treatment. While single case experiences may provide valuable reference for later decision-making, well-documented clinical experience with off-label targeted treatments is limited to a few patients. Here, we report a case of a 31-year-old female UrC patient who underwent intensive therapy with three surgeries and five lines of systemic treatments, including chemo-, checkpoint inhibitor and tyrosine kinase inhibitor therapies. In addition, next-generation sequencing (NGS) analysis and an ex vivo drug-screening analysis were performed on patient-derived tumor cells and the results were implemented into the therapeutic decision-making. Finally, serum carcinoembryonic antigen (CEA) levels proved to be helpful for therapy monitoring during the whole follow-up period.
Environmental Impact of Xenobiotic Aromatic Compounds and Their Biodegradation Potential in Comamonas testosteroni
Authors: Li Yapeng , Fan Huixin , Li Boqiao , Liu Xiaobo
Published: December 2024

Xenobiotic aromatic compounds are the raw materials of necessities in modern life, such as plastics, pesticides, and antibiotics. To meet the global requirements, their production and consumption have continually increased, and thus, the vast amount of waste generated results in prominent environmental pollution. Fortunately, some microorganisms (e.g., Comamonas spp.) can specially use these pollutants as substrates for growth, allowing for the development of bioremediation technology to achieve sustainable development goals. Here, we describe common xenobiotic aromatic compounds used in our daily life, discuss their impact on the environment, and review their biodegradation strategies by Comamonas testosteroni, as an example. Finally, we argue that microbiome engineering opens up the avenue to future biofilm-based biodegradation technology to improve aromatic compound bioremediation.
Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy
Authors: Bairqdar Ahmad , Karitskaya Polina E. , Stepanov Grigory A.
Published: December 2024

CRISPR–Cas technology has transformed the field of gene editing, opening new possibilities for treatment of various genetic disorders. Recent years have seen a surge in clinical trials using CRISPR–Cas-based therapies. This review examines the current landscape of CRISPR–Cas implementation in clinical trials, with data from key registries, including the Australian New Zealand Clinical Trials Registry, the Chinese Clinical Trial Register, and ClinicalTrials.gov. Emphasis is placed on the mechanism of action of tested therapies, the delivery method, and the most recent findings of each clinical trial.
Design, Synthesis, and Biological Evaluation of Novel Urea-Containing Carnosic Acid Derivatives with Anticancer Activity
Authors: Moura Sara P. S. P. , Marín Silvia , Rufino Ismael , Guedes Rita C. , Cascante Marta , Salvador Jorge A. R.
Published: December 2024

A series of novel carnosic acid 1 derivatives incorporating urea moieties at the C-20 position was synthesized and evaluated for their antiproliferative activity against the HCT116 colorectal cancer cell line. Most derivatives demonstrated enhanced antiproliferative activity compared to that of carnosic acid 1. The most promising derivatives were tested in other colorectal cancer cell lines (SW480, SW620, and Caco-2), melanoma (A375), and pancreatic cancer (MiaPaca-2). Derivative 14 consistently demonstrated the highest activity across all tested cancer cell lines, showing selectivity for cancer cells over normal cells. Further investigation of the mechanism of action in SW480 cells revealed that compound 14 induced cell cycle arrest at the G0/G1 phase by downregulating CDK4 and CDK6. Molecular docking studies revealed that compound 14 established several interactions with key residues in the active site of CDK6. Additionally, compound 14 also reduced ROS production. In summary, our results strongly indicate that compound 14 has potential as a lead compound in the development of innovative anticancer drugs.
The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling
Authors: Podyacheva Ekaterina , Snezhkova Julia , Onopchenko Anatoliya , Dyachuk Vyacheslav , Toropova Yana
Published: December 2024

Doxorubicin (DOX), a cornerstone chemotherapeutic agent, effectively combats various malignancies but is marred by significant cardiovascular toxicity, including endothelial damage, chronic heart failure, and vascular remodeling. These adverse effects, mediated by oxidative stress, mitochondrial dysfunction, inflammatory pathways, and dysregulated autophagy, underscore the need for precise therapeutic strategies. Emerging research highlights the critical role of microRNAs (miRNAs) in DOX-induced vascular remodeling and cardiotoxicity. miRNAs, such as miR-21, miR-22, miR-25, miR-126, miR-140-5p, miR-330-5p, miR-146, miR-143, miR-375, miR-125b, miR-451, miR-34a-5p, and miR-9, influence signaling pathways like TGF-β/Smad, AMPKa/SIRT, NF-κB, mTOR, VEGF, and PI3K/AKT/Nrf2, impacting vascular homeostasis, angiogenesis, and endothelial-to-mesenchymal transition. Despite existing studies, gaps remain in understanding the full spectrum of miRNAs involved and their downstream effects on vascular remodeling. This review synthesizes the current knowledge on miRNA dysregulation during DOX exposure, focusing on their dual roles in cardiovascular pathology and tumor progression. Strategies to reduce DOX cardiotoxicity include modulating miRNA expression to restore signaling balance, targeting pro-inflammatory and pro-fibrotic pathways, and leveraging miRNA inhibitors or mimics. This review aims to organize and integrate the existing knowledge on the role of miRNAs in vascular remodeling, particularly in the contexts of DOX treatment and the progression of various cardiovascular diseases, including their potential involvement in tumor growth.
Acetylated Globotetraose (Ac-Gb4) Suppresses Triple-Negative Breast Cancer Through FAK/AKT Signaling Pathway
Authors: Lee Yung-Kuo , Sehar Misbah , Botcha Lavanya , Chuang Po-Kai
Published: December 2024

Triple-negative breast cancer (TNBC) remains a significant therapeutic challenge due to its unresponsiveness to hormone and HER2-targeted treatments. This study investigated the potential of acetylated globotetraose (Ac-Gb4) as a novel therapeutic approach targeting glycolipid-mediated signaling in breast cancer cells. We synthesized acetylated globotetraose (Gb4) to enhance its membrane permeability while preserving its biological recognition properties. Flow cytometry analysis revealed that Ac-Gb4 treatment significantly decreased SSEA3 and SSEA4 expression in MDA-MB-231 breast cancer cells, which are Globo-H-negative cells. Notably, Ac-Gb4 demonstrated selective cytotoxicity against cancer cells by significantly reducing proliferation and inducing apoptosis in MDA-MB-231 cells while sparing hTERT-HME1 normal breast epithelial cells. Mechanistic studies through Western blot analysis revealed that Ac-Gb4 simultaneously modulated multiple signaling pathways, including FAK cleavage, reduced AKT expression, and increased caspase-3 activation, particularly at the 4 mM concentration. These molecular changes correlated with decreased cancer cell invasion capability in a dose-dependent manner. Our findings demonstrated that Ac-Gb4 effectively targeted breast cancer cells through the modulation of critical signaling pathways involved in cell survival and invasion while maintaining a minimal impact on normal cells. This anti-cancer activity suggests that Ac-Gb4 represents a promising therapeutic candidate for breast cancer treatment, particularly for aggressive subtypes such as TNBC.
Upregulation of Insulin and Ecdysone Signaling in Relation to Diapause Termination in Bombyx mori Eggs Exposed to 5 °C
Authors: Gu Shi-Hong , Lin Pei-Ling
Published: December 2024

In the present study, we investigated the possible correlation between insulin/ecdysone signaling and chilling-induced egg diapause termination in Bombyx mori. Changes in insulin (bombyxin-Z1) and ecdysteroid-phosphate phosphatase (EPPase) gene expression levels in chilled eggs (whose diapause had been terminated by chilling to 5 °C for 90 days) exhibited no significant increase after being transferred to 25 °C, which differed from both non-diapause eggs and HCl-treated eggs. We further compared the differential temporal expressions of insulin (bombyxin-A6, -Y1, and -Z1), ecdysone signaling (EPPase and E75A), and metabolic-related (trehalose transporter 1 (Tret1) and trehalase 1 (Treh1)) as well as sorbitol dehydrogenase 2 (SDH2) genes between chilled eggs and eggs kept at 25 °C. Our results showed that all gene expressions remained at very low levels in eggs kept at 25 °C. However, in chilled eggs, differential temporal changes were detected according to different genes, with bombyxin-A6 and EPPase gene expression levels being maintained at relatively constant, high levels. Higher expression levels of the E75A, Tret1, and Treh1 genes were also detected in chilled eggs. Expressions of the SDH2 and bombyxin-Z1 genes decreased during the first 15 days and then increased between days 30 and 90 of chilling. Ecdysteroid levels and phosphorylation of glycogen synthase kinase (GSK)-3β, a downstream target of insulin signaling, were maintained at relatively higher levels in chilled eggs. These results suggested that due to relatively higher insulin and ecdysone signaling levels in chilled eggs, relatively higher glucose metabolism was sustained, leading to the continued depletion of metabolic reserves. On day 30 of chilling, as a means to adjust nutrient requirements and maintain embryonic nutrient homeostasis, SDH2 gene expression began to increase, followed by increased expression of the bombyxin-Z1 gene. Along with high expressions of the bombyxin-Z1 and SDH2 genes, a decreased sorbitol level was suggested to eventually terminate diapause in B. mori eggs. To our knowledge, this is the first study to demonstrate the correlation between insulin/ecdysone signaling and chilling-induced embryonic diapause termination.
Diagnostic Accuracy of MRI for Orbital and Intracranial Invasion of Sinonasal Malignancies: A Systematic Review and Meta-Analysis
Authors: Abdullaeva Umida , Pape Bernd , Hirvonen Jussi
Published: December 2024

Background/Objectives: In this study, we review the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting orbital and intracranial invasion of sinonasal malignancies (SNMs) using histopathological and surgical evidence as the reference standard. Methods: A systematic search of studies in English was conducted in MEDLINE and Embase, limited to articles published since 1990. We included studies using preoperative MRI to detect the intracranial and orbital invasion of SNMs, with histological or surgical confirmation as the reference standard, and reported patient numbers in each class as required to assess diagnostic accuracy. The outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed with the Higgins inconsistency test (I2). Results: Seven original articles with 546 subjects were included in the review, with six included in the meta-analysis. The pooled overall accuracy for orbital invasion was higher at 0.88 (95% CI, 0.75–0.94) than that for intracranial invasion at 0.80 (95% CI, 0.76–0.83). The meta-analytic estimates and their 95% confidence intervals were as follows for intracranial/orbital invasion: sensitivity 0.77 (0.69–0.83)/0.71 (0.40–0.90); specificity 0.79 (0.74–0.83)/0.91 (0.78–0.97); PPV 0.76 (0.64–0.85)/0.78 (0.61–0.88); and NPV 0.82 (0.72–0.89)/0.90 (0.63–0.98). Substantial heterogeneity was observed in the Higgins inconsistency test (I2) for orbital invasion (84%, 83%, and 93% for sensitivity, specificity, and NPV, respectively). Conclusions: MRI yielded moderate-to-high diagnostic accuracy for intracranial and orbital invasion, despite some limitations leading to false diagnoses. Loss of the hypointense zone on postcontrast MRI was found to predict dural invasion. Infiltration of the extraconal fat beyond the periorbita was found to be an MRI feature of orbital invasion.
No Obesity Paradox for Health-Related Quality of Life in Patients with Heart Failure and Reduced Ejection Fraction: Insights from the VIDA Multicenter Study
Authors: Cassadó-Valls Paula , Enjuanes Cristina , Anguita Manuel , Formiga Francesc , Almenar Luis , Crespo-Leiro María G. , Manzano Luis , Muñiz Javier , Chaves José , Hidalgo Encarna , Ramos-Polo Raúl , Yun Sergi , José-Bazán Núria , Moliner Pedro , Comín-Colet Josep
Published: December 2024

Background and Objectives: Previous studies showed that, paradoxically, obese patients with heart failure (HF) have better clinical outcomes compared to overweight, normal, or underweight patients. Scientific societies emphasize the importance of integrating quality of life (QoL) assessment in cardiovascular care. However, the association between QoL and weight remains understudied. Given the significant correlation between HF survival and QoL, it is essential to assess how obesity impacts patient-reported outcomes in this clinical setting. Methods: This cross-sectional multicenter study in 1028 HF patients with reduced ejection fraction (HFrEF) aims to evaluate the association between obesity and QoL, and whether the obesity paradox holds for HF patients regarding QoL. Specific and generic QoL questionnaires were administered alongside clinical parameters like body mass index (BMI) and body adiposity estimator (BAE). Results: Obese compared to non-obese reported worse QoL. In the adjusted linear regression models, neither BMI nor obesity were associated with QoL. Generalized additive models confirmed a strong non-parametric association between BMI, subdomain scores from Kansas City Cardiomyopathy Questionnaire (KCCQ) (OSS p = 0.004, CSS p = 0.006, TSS p = 0.02), and summary measurements of EQ-5D (EQ-5D index p = 0.003, visual analogue scale (VAS) p = 0.01). In contrast, BAE showed a statistically significant linear relation among QoL (OSS p ≤ 0.001, CSS p ≤ 0.001, TSS p ≤ 0.001) and EQ-5D summary measurements (EQ-5D index p ≤ 0.001, VAS p ≤ 0.001). Conclusions: Overall, obese patients have worse QoL; therefore, obesity cannot be considered a protective factor in terms of QoL in established HF.
Rheumatologic Perspectives on Sarcoidosis: Predicting Sarcoidosis-Associated Arthritis Through Comprehensive Clinical and Laboratory Assessment
Authors: Ekin Ali , Mısırcı Salim , Sertkaya Oğuzhan , Coşkun Belkıs Nihan , Yağız Burcu , Dalkılıç Ediz , Pehlivan Yavuz
Published: December 2024

Background/Objectives: The primary aim of our study was to evaluate the demographic, clinical, and laboratory characteristics of sarcoidosis patients with musculoskeletal symptoms; investigate the relationship between arthritis development and various laboratory parameters (such as vitamin D, liver enzymes, and ACE levels); and compare the sarcoidosis-associated arthritis cases with those without. We also explored the factors influencing arthritis development and the role of biopsy in diagnosing sarcoidosis within rheumatology practice. Methods: This retrospective study analyzed 147 sarcoidosis patients from 2000 to 2024, categorized by the presence (n = 45) or absence (n = 102) of arthritis. Demographic, clinical, and laboratory data, including biopsy results, were collected and compared. Results: The mean age was 56.02 ± 11.21 years, with a mean disease duration of 134.33 ± 56.98 months. Females constituted 86.4% of the cohort. All of the patients presented musculoskeletal involvement. Pulmonary involvement was present in 93.7% of cases, and extrapulmonary involvement included the skin (21.20%), the eyes (14.30%), and peripheral lymphadenopathy (10.6%). Methotrexate was the most common treatment after corticosteroids. In the arthritis group, diabetes mellitus was more frequent (p = 0.024), the GGT levels were higher (p = 0.044), and the 25-hydroxyvitamin D levels (p = 0.002) and the DLCO Adj (p = 0.039) were lower. Multivariable regression showed diabetes mellitus (p = 0.028, OR: 4.805, 95% CI: 1.025–22.518) and low 25-hydroxyvitamin D levels (p = 0.034, OR: 0.914, 95% CI: 0.841–0.993) as factors influencing arthritis development. The other parameters showed no significant differences. Conclusions: This study identified significant clinical, demographic, and laboratory differences between sarcoidosis patients with and without arthritis. The patients with sarcoidosis-associated arthritis exhibited a higher frequency of diabetes mellitus, lower levels of 25-hydroxyvitamin D, and elevated GGT levels. Additionally, the lower DLCO values in the patients with arthritis indicate a more severe impact on pulmonary function, underscoring the importance of comprehensive pulmonary evaluation in this subgroup.
Transcutaneous Kilohertz High-Frequency Alternating Current at 10 kHz for Upper-Limb Tremor in People with Parkinson’s Disease: A Double-Blind, Randomized, Crossover Study
Authors: Fernández-Pérez Juan J. , Avendaño-Coy Juan , Serrano-Muñoz Diego , Oliveira Barroso Filipe , Montero-Pardo Cristina , López-Moreno Beatriz , Lerín-Calvo Alfredo , Romero Muñoz Juan P. , Gómez-Soriano Julio
Published: December 2024

Background/Objectives: Preclinical studies have evidenced a peripheral nerve blockade with kilohertz high-frequency alternating current (KHFAC) stimulation. It could have a potential effect on aberrant nerve hyperactivity, such as tremor in people with Parkinson’s disease (PwPD). The objective was to investigate the effects of transcutaneous KHFAC at 10 kHz compared with sham intervention on tremor modulation, upper limb motor function, and adverse events in PwPD. Methods: This randomized, double-blind, crossover trial included PwPD, who received transcutaneous KHFAC and sham interventions, within a 48 h washout period. Measurements were taken pre-intervention, during, immediately after, and 10 min post-intervention. The main outcomes were rest, postural, and kinetic tremor acceleration. Secondary outcomes were handgrip strength, nine-hole peg test (NHPT), movement onset time, and adverse events. Results: Sixteen PwPD were analyzed. Kinetic tremor diminished only in active treatment from baseline at post-intervention (−32.3% (SD 63.3); p = 0.03) and 10 min after intervention (−38.9% (SD 60.3); p = 0.03). Active treatment showed a greater reduction in kinetic tremor at post-treatment compared to sham (−58.7% SD 123; p = 0.055) close to reaching statistical significance. Only active intervention diminished movement onset time at post-intervention (−26.9% (SD 28.3); p = 0.04). Active intervention diminished handgrip strength compared to sham intervention during the stimulation (−6.6% (SD 10.0); p = 0.02). No relevant adverse effects were reported. Conclusions: KHFAC stimulation at 10 kHz appeared safe and showed potential benefits for reducing kinetic tremor in PwPD. The transient reduction in grip strength suggested an effect on alpha-motoneurons. However, further studies with larger sample sizes are necessary to confirm these findings.
The Effect of Bisphenol and Its Cytotoxicity on Female Infertility and Pregnancy Outcomes: A Narrative Review
Authors: Drakaki Eirini , Stavros Sofoklis , Dedousi Dimitra , Potiris Anastasios , Mavrogianni Despoina , Zikopoulos Athanasios , Moustakli Efthalia , Skentou Charikleia , Thomakos Nikolaos , Rodolakis Alexandros , Drakakis Peter , Domali Ekaterini
Published: December 2024

Bisphenols, particularly bisphenol A (BPA), are among the most thoroughly investigated endocrine disrupting chemicals (EDCs). BPA was the first synthetic estrogen to be identified, exerting its estrogenic effects through interaction with human estrogen receptors (ERs). The aim of the present narrative review is to summarize the most recent literature regarding the adverse effects of bisphenols on female fertility and pregnancy outcomes. A review of the literature in the PubMed/Medline and Scopus databases was conducted in November 2024 and 15 studies were included in the present review. BPA levels were higher in women with diminished ovarian reserve, polycystic ovary syndrome, and recurrent miscarriages. Furthermore, one study showed a significant association between BPA levels and the onset of gestational diabetes mellitus. Higher levels of BPA are associated with disruptions to the female reproductive system, such as ovarian function, reduced number of antral follicles, and lower anti-Müllerian hormone (AMH) levels. Bisphenols A and S were associated with an increased risk of developing gestational diabetes mellitus. Bisphenols A and F were correlated with an increased risk of lower birth weight and bisphenol F seemed to be associated with an increased risk of preterm delivery. Ultimately, further research is necessary to fully understand the extent of the harmful effects that bisphenols have separately and as mixtures on the female reproductive system.
The Role of Scanning Electron Microscopy in the Evaluation of Conjunctival Microvilli as an Early Biomarker of Ocular Surface Health: A Literature Review
Authors: Troisi Mario , Del Prete Salvatore , Troisi Salvatore , Del Prete Antonio , Bellucci Carlo , Marasco Daniela , Costagliola Ciro
Published: December 2024

Microvilli are bristle-like protuberances of the plasma membrane, which express the vitality of mucous and epithelial cells; their alteration indicates a condition of cellular suffering in a predictive sense, making it possible to establish how much an inflammatory state or toxic conditions affect cellular functionality. In this article, the authors evaluate the applications of scanning electron microscopy (SEM) examination to impression cytology (IC) of the bulbar conjunctiva for the assessment of microvillar alteration as an early ultrastructural indicator of ocular surface health. This method offers several advantages, starting with its simplicity: it involves the non-invasive application of a strip of bibulous paper to the bulbar or tarsal conjunctiva. Unlike conjunctival or corneal biopsies, which are surgical procedures, this technique is far less invasive and more comfortable for the patient. It also provides a more clinically relevant in vivo assessment compared to studies on cultured cell lines, which are mostly limited to scientific research and may not accurately reflect real-world conditions. This makes it an effective, repeatable, and patient-friendly option for detecting early pathological alterations of the ocular surface. It also represents a useful tool for evaluating the efficacy of topical drugs and the toxic effects of external factors and ophthalmic or systemic diseases. Finally, it allows for obtaining accessory information relating to goblet cells, the presence of inflammatory infiltrate, or any pathogens.
How Close Are We to Patient-Side Troponin Testing?
Authors: Goldberg Aaron , McGrath Samuel , Marber Michael
Published: December 2024

Laboratory-based high-sensitivity cardiac troponin testing has been the pillar for emergency stratification of suspected acute coronary syndrome for well over a decade. Point-of-care troponin assays achieving the requisite analytical sensitivity have recently been developed and could accelerate such assessment. This review summarises the latest assays and describes their potential diverse clinical utility in the emergency department, community healthcare, pre-hospital, and other hospital settings. It outlines the current clinical data but also highlights the evidence gap, particularly the need for clinical trials using whole blood, that must be addressed for safe and successful implementation of point-of-care troponin analysis into daily practice. Additionally, how point-of-care troponin testing can be coupled with advances in biosensor technology, cardiovascular screening, and triage algorithms is discussed.
Emergencies in Hematology: Why, When and How I Treat?
Authors: Duminuco Andrea , Del Fabro Vittorio , De Luca Paola , Leotta Dario , Limoli Miriana Carmela , Longo Ermelinda , Nardo Antonella , Santuccio Gabriella , Petronaci Alessandro , Stanzione Gaia , Di Raimondo Francesco , Palumbo Giuseppe Alberto
Published: December 2024

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure. Sickle cell crisis, a common complication in sickle cell disease, results from vaso-occlusion, leading to acute pain and tissue ischemia. Tumor lysis syndrome, reported in cases of rapid destruction of cancer cells, causes electrolyte imbalances and acute kidney injury. Acute transfusion reactions, fundamental in hematological conditions, can range from mild allergic responses to severe hemolysis and shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation and bleeding, is commonly triggered by hematological malignancies, common in the first phases of acute promyelocytic leukemia. Recently, in the era of bispecific antibodies and chimeric antigen receptor T cells, cytokine release syndrome is a manifestation that must be recognized and promptly treated. Understanding the pathophysiology, recognizing the clinical manifestations, and ensuring adequate diagnostic strategies and management approaches for each condition are central to early intervention in improving patient outcomes and reducing mortality.
Tympanic Pre-Operative Electrically Evoked Auditory Late Response (TympEALR) as an Alternative to Trans-Tympanic Tests Using Anesthesia in Cochlear Implant Candidacy
Authors: Polterauer Daniel , Neuling Maike , Simon Florian
Published: December 2024

Background/Objectives: Before a cochlear implant is considered, patients undergo various audiological tests to assess their suitability. One key test measures the auditory brainstem response (ABR) to acoustic stimuli. However, in some cases, even with maximum sound stimulation, no response is detected. Methods: The promontory test involves electrical stimulation near the auditory nerve, allowing patients to associate the sensation. Ideally, the electrode is placed in the middle ear after opening the eardrum. This method, along with trans-tympanic electrically evoked ABR in local anesthesia (LA-TT-EABR) and the cortical equivalent (LA-TT-EALR), helps assess the auditory nerve’s existence and excitability. The TympEALR test, utilizing a “tympanic LA-TT-EALR”, provides an alternative measurement. Previous research has shown the possibility of deriving brainstem and cortical potentials through trans-tympanic electrical stimulation, allowing for objective assessment of the auditory nerve’s integrity and potentially objectifying patient sensations. Results: Sixteen patients have been tested using TympEALR. In seven of these, we found a positive response. The morphology was similar to other electrically evoked cortical auditory responses (EALR), e.g., using cochlear implants or trans-tympanic stimulation electrodes. We observed a higher influence of electrical artifacts than in other EALRs. Conclusions: TympEALR showed positive results in nearly half of the study participants, potentially avoiding invasive procedures. TympEALR can be a valuable alternative to trans-tympanic methods. More research is needed to determine if a negative result suggests against cochlear implantation.
Automatic Recognition of Motor Skills in Triathlon: A Novel Tool for Measuring Movement Cadence and Cycling Tasks
Authors: Chesher Stuart M. , Martinotti Carlo , Chapman Dale W. , Rosalie Simon M. , Charlton Paula C. , Netto Kevin J.
Published: December 2024

Background/Objectives: The purpose of this research was to create a peak detection algorithm and machine learning model for use in triathlon. The algorithm and model aimed to automatically measure movement cadence in all three disciplines of a triathlon using data from a single inertial measurement unit and to recognise the occurrence and duration of cycling task changes. Methods: Six triathletes were recruited to participate in a triathlon while wearing a single trunk-mounted measurement unit and were filmed throughout. Following an initial analysis, a further six triathletes were recruited to collect additional cycling data to train the machine learning model to more effectively recognise cycling task changes. Results: The peak-counting algorithm successfully detected 98.7% of swimming strokes, with a root mean square error of 2.7 swimming strokes. It detected 97.8% of cycling pedal strokes with a root mean square error of 9.1 pedal strokes, and 99.4% of running strides with a root mean square error of 1.2 running strides. Additionally, the machine learning model was 94% (±5%) accurate at distinguishing between ‘in-saddle’ and ‘out-of-saddle’ riding, but it was unable to distinguish between ‘in-saddle’ riding and ‘coasting’ based on tri-axial acceleration and angular velocity. However, it displayed poor sensitivity to detect ‘out-of-saddle’ efforts in uncontrolled conditions which improved when conditions were further controlled. Conclusions: A custom peak detection algorithm and machine learning model are effective tools to automatically analyse triathlon performance.
Energy Efficient Jet Polishing via Electrolytic Plasma Enhances Corrosion Resistance in Stainless Steel
Authors: Ghezri Adel , Pratama Killang , Scholl Yan , Küenzi Alexander , Nelis Thomas , Burger Jürgen , Bessire Cedric
Published: December 2024

This study systematically compares the surface polishing performance and finishing results of the following two different electrolytic plasma polishing technologies on stainless steel AISI 316L: (i) plasma electrolytic polishing (PEP) and (ii) plasma electrolytic polishing jet (PEP-Jet). The two techniques are compared against an industrial standard polishing method, electropolishing (EP). For comparable energy density consumption, the samples treated with the PEP-Jet technique showed the highest removal rate, up to three times less than the initial roughness, resulting in the highest surface roughness reduction from Sa = 249 nm to Sa = 81 nm. Microstructure characterization of samples treated using PEP-Jet also showed well-defined crystalline grain boundaries with a distinct appearance of predominantly inter-crystalline structures within individual grains, which is uncommon with EP techniques. The surfaces treated using PEP-Jet exhibited the lowest corrosion rate of 6.79×10−5 mm/year, and no signs of areal corrosion were detected in the performed corrosion tests in contrast with the other samples and their respective treatments. The comparative analysis revealed that the high ionic current delivered by the electrolyte jet flow in the PEP-Jet process effectively stabilizes the plasma at the contact zone, thereby enhancing the plasma polishing of austenitic stainless steel samples. The efficacy of this method has been demonstrated in terms of reducing energy consumption and enhancing corrosion resistance in comparison with (PEP) and (EP) as state-of-the-art processes in corrosive environments of high-alloyed steel.