bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in Amplicon-Based DNA NGS Identification of MET Exon 14 Skipping Events in Non-Small Cell Lung Cancers
Authors: Jurkiewicz Magdalena , Yeh Raymond , Shu Catherine A. , Hsiao Susan J. , Mansukhani Mahesh M. , Saqi Anjali , Fernandes Helen
Published: February 2025

Introduction: MET Exon 14 skipping alterations are drivers of non-small cell lung carcinoma (NSCLC) with responses to tyrosine kinase inhibitors. Amplicon-based DNA NGS assays (DNA NGSs) for the detection of METex14 skipping can yield false-negative results. We examined the efficacy of METex14 skipping with a DNA NGS and reflex RNA-based NGS (RNA NGS) strategy. Materials and Methods: Clinical cases with definitive or suspected lung adenocarcinoma (LungCa), lacking driver mutations with targeted DNA NGS, underwent the RNA NGS to identify oncogenic drivers. Samples with METex14 skipping identified on reflex RNA NGSs were confirmed with Sanger sequencing. Results:METex14 skipping events were detected in 22/762 (2.9%) samples by DNA NGS. RNA NGS identified 10 additional samples, for an overall frequency of 32/762 (4.1%). All 22 METex14 DNA variants affected the donor splice site. Sanger sequencing revealed that missed METex14 variants were largely deletions spanning the ~30 bp intronic region upstream of the splice acceptor site. The failure of DNA NGS to detect all METex14 mutants was due to a lack of coverage of the 3′ splice acceptor site of intron 13, branch point, and polypyrimidine tract. Conclusions: Modification of amplicon-based DNA hotspot assays, with primers that cover both donor and acceptor splice sites, can identify a larger number of METex14 skipping events. Clinical data show that patients with advanced NSCLC and METex14 variants responded to targeted therapy.
Research on Energy Dissipation Mechanism of Hump Characteristics Based on Entropy Generation and Coupling Excitation Mechanism of Internal Vortex Structure of Waterjet Pump at Hump Region
Authors: Liu Min , Long Yun , Yin Hong , Tian Chenbiao , Zhong Jinqing
Published: February 2025

High-speed mixed-flow and axial-flow pumps often exhibit hump or double-hump patterns in flow–head curves. Operating in the hump region can cause flow disturbances, increased vibration, and noise in pumps and systems. Variable-speed ship navigation requires waterjet propulsion pumps to adjust speeds. Speed transitions can lead pumps into the hump region, impacting efficient and quiet operation. This paper focuses on mixed-flow waterjet propulsion pumps with guide vanes. Energy, entropy production, and flow characteristic analyses investigate hump formation and internal flow properties. High-speed photography in cavitation experiments focuses on increased vibration and noise in the hump region. This study shows that in hump formation, impeller work capacity decreases less than internal fluid loss in the pump. These factors lead to an abnormal increase in the energy curve. The impeller blades show higher pressure at peak conditions than in valley conditions. Valley conditions show more pressure and velocity distribution variance in impeller flow passages, with notable low-pressure areas. This research aids in understanding pump hump phenomena, addressing flow disturbances, vibration, noise, and supporting design optimization.
Identification of Duplicate Features Among Universal Hydrographic Data Models to Enhance Interoperability Through Natural Language Processing
Authors: Jeong Hyewon , Lee Changui
Published: February 2025

In the field of geographic information, research on identifying and integrating duplicate data for quality improvement has been actively conducted, contributing to enhancing the reliability of spatial information-based decision-making. The International Hydrographic Organization (IHO) has standardized hydrographic data through a universal hydrographic data model in the hydrographic field. As multiple institutions are independently modeling the data, duplication is occurring in the process of defining ‘features’, which abstract real-world objects as classes. Quality degradation due to these duplicate features can cause confusion in the decision-making process of smart ships, potentially threatening safe navigation. Previous studies in the hydrographic field have identified duplicate features manually, but continuous updates and an increasing number of products have made it difficult to identify all duplicate features. This study proposes a method to identify duplicate features defined in data models using deep learning-based natural language processing models. Through the proposed method, 313 additional duplicate features that were not previously discovered were identified. This efficient approach to identifying duplicate features is anticipated to support interoperability processes, thereby contributing to the stable operation of smart ships and the enhancement of maritime safety.
Impact of Enhanced Recovery After Surgery with Neuromuscular Monitoring and Sugammadex on Healthcare Costs and Effectiveness of Recovery in Patients Following Anterior Cervical Spine Discectomy
Authors: Hsu Hung-Te , Chen Szu-Yu , Huang Yu-Kai , Cheng Kuang-I , Weng Shih-Feng , Wu Zhi-Fu
Published: February 2025

Background/Objectives: Anterior cervical spine surgery (ACSS) is an effective surgical procedure used to treat degenerative cervical spine disease. Enhanced recovery after surgery (ERAS) is a new and promising paradigm for ACSS. The purpose of this study is to investigate the role of neuromuscular monitoring with sugammadex in the ERAS protocol, which had not been confirmed in ACSS. Methods: In this retrospective study, the electronic medical records of patients aged 20 to 80 years who had undergone first-time ACSS performed in the period from 1 December 2018 to 31 December 2023 were reviewed. Patients were divided into ERAS and non-ERAS groups. Inverse probability of treatment weighting (IPTW) was used to balance differences between the groups. Statistical analyses were conducted using SPSS 20, including independent samples t-tests, chi-square tests, linear regression, and logistic regression. Results: A total of 394 patients were included in this study: 163 in the non-ERAS group and 231 in the ERAS group. In the ERAS group, significant reductions were observed in several key outcomes compared with the non-ERAS group: LOS was reduced by 0.62 days (p < 0.001), hospital costs were lowered by NTD 13,174.40 (p < 0.001), ventilator time was decreased by 149.40 min (p < 0.001), time to first oral intake was shortened by 4.71 h (p < 0.001), and time to first ambulation was reduced by 8.00 h (p < 0.001). No significant differences in complication rates were observed between the two groups. Conclusions: The ACSS-tailored ERAS pathway with NMM and sugammadex can reduce LOS, cost, and speed of patient recovery without increasing complications.
Land Use Changes, Environmental Impact and Socio-Economic Effects of Road Infrastructure Mega Projects: The Combined Case of the Rio–Antirio Bridge and the Ionian Road in Greece
Authors: Kantianis Dimitrios , Polyzos Serafeim , Krabokoukis Thomas
Published: February 2025

The research aims at studying land use changes, the environmental impact and socio-economic effects from the construction of major road transport infrastructure projects. The methodology adopted herein includes a review of the relevant literature to examine the relationship between infrastructure provision and associated positive or negative impacts on land, environment, society and economy. Statistical data mainly from the Hellenic Statistical Authority and useful informational data from relevant research and recent studies were collected and processed in order to evaluate the overall effect of the two major road projects Gefyra “Charilaos Trikoupis” (Rio–Antirio Bridge) and Ionia Odos (Ionian Road) in the Regions of Dytiki Ellada (Western Greece), Ipeiros (Epirus) and Ionioi Nisoi (Ionian Islands). The descriptive statistical analysis indicates that positive impacts include the following: transport time savings and road safety improvement; increased commercial imports/exports activity; increased private building activity and tourist traffic/employment; and intensified truck traffic at the port of Igoumenitsa. Conversely, negative impacts involve: less arable agricultural land; increased whilst tolerable environmental pollution; and a general reduction in all types of traffic activity at the port of Patras. From the quantitative analysis using the analytic hierarchy process (AHP), it emerged that the most overall benefitted region is the Ionian Islands, followed by Epirus and Western Greece. The general conclusion from the research seems to support the theoretical approaches and related studies: transport infrastructure is an important condition but not a guarantee of regional development.
A Systematic Review of Evidence-Based Alternative Models of Incarceration
Authors: Suʻesuʻe Anamalia , Pilger Dylan , Riley Lorinda
Published: February 2025

While much of the American justice system utilizes punitive models of sentencing and incarceration, restorative justice (RJ) approaches provide a holistic alternative to wrongdoing, viewing offenses in terms of relationships and paying particular attention to victim and community needs. These alternative RJ approaches have been shown to decrease recidivism and align with the values of those who have been most impacted by mass incarceration, including Indigenous populations. The purpose of this systematic review is to provide an overview of alternative models of incarceration utilizing RJ principles that could be adapted for a largely Indigenous population.
Efficacy of Ultrasound-Guided Injections of Type I Collagen-Based Medical Device for Greater Trochanteric Pain Syndrome: A Pilot Study
Authors: Randelli Filippo , Fioruzzi Alberto , Mazzoleni Manuel Giovanni , Radaelli Alessandra , Rahali Leila , Verga Lucia , Menon Alessandra
Published: February 2025

Background: Greater Trochanteric Pain Syndrome (GTPS) is a frequent clinical condition characterized by acute or chronic pain in the lateral region of the hip. This condition is primarily due to gluteus minimus and medius tendinopathy. Swine-derived type I collagen has shown a positive effect on tenocytes through in vitro studies and on tendinopathies in clinical studies. This pilot study aims to evaluate the clinical effects of swine-derived type I collagen injections on pain, hip function, and strength in GTPS patients. Methods: The study group was treated with three ultrasound-guided swine-derived type I collagen injections once a week for three consecutive weeks. The primary endpoint was pain reduction of at least 3 points on the Numeric Rating Scale (NRS) at ten weeks. Secondary endpoints were NRS average reduction at rest and palpation, modified Harris Hip Score (mHHS), abductor strength, and magnetic resonance imaging (MRI) improvement at six months. Results: 52 patients were screened, 47 enrolled, and 43 completed the study. The primary endpoint was reached by 60.5% of the patients. All secondary endpoints were also reached with statistical significance. Neither early nor late adverse effects were found. Conclusions: In this pilot study, ultrasound-guided peritrochanteric swine-derived type I collagen injections are safe and effective for most patients with GTPS included in the study. Further and more extensive confirmatory investigation studies with a longer follow-up are needed to confirm this pilot study’s results and the clinical benefit’s persistence.
Traumatic Brain Injury Guideline Implementation at a University Hospital in Saudi Arabia
Authors: AlShahwan Nawaf , Aldeligan Saleh Husam , AlQahtani Abdulaziz S. , Sallam Moath Shaher , Alqusiyer Abdulaziz , Fallatah Ahmed A. , Alburakan Ahmed , Mashbari Hassan , Albdah Abdullah , Nouh Thamer
Published: February 2025

Traumatic Brain Injuries (TBIs) pose a significant global health burden, with high mortality and long-term disability rates. This retrospective cohort study investigates the implementation and impact of the Brain Trauma Foundation (BTF) guidelines on TBI management in a Saudi Arabian tertiary care center. Data from the pre-implementation (2012) and post-implementation (2022) of BTF guidelines periods were compared. The patient demographics, injury severity, guideline adherence, and outcomes were analyzed. The results revealed a 33% increase in severe TBI cases from 2012 to 2022, possibly due to the development of a well-established trauma system designed to manage such cases. More importantly, implementing the BTF guidelines led to a marked improvement in patient outcomes. Compliance with guidelines, including the avoidance of hypoxia and hypotension, hyperosmolar therapy, and DVT prophylaxis significantly increased post-implementation. Mortality rates decreased from 45.4% to 14.2%, accompanied by a reduction in the intensive care unit (ICU) length of stay and an increase in the hospital length of stay. A comparison with international trauma centers highlights the importance of protocol-based management in improving the TBI outcomes and reducing the mortality—factors such as specialist-led care, institutional policies, and increased resources influenced guideline adherence and patient care. This study underscores the critical role of evidence-based guidelines in optimizing TBI management and emphasizes the need for their widespread implementation in clinical practice. In conclusion, this study demonstrates the substantial impact of BTF guidelines on enhancing TBI patient outcomes in a Saudi Arabian tertiary care center. The implementation of these guidelines resulted in a significant reduction in mortality and in an improved adherence to the best practices in TBI management, highlighting the importance of evidence-based protocols in optimizing patient care and outcomes.
A Micro-Nodal Tungsten-Rhenium Thin-Film Thermocouple Based on Electrohydrodynamic Printing
Authors: Hu Shuntao , Chen Jun , Gong Shigui , Li Ying , Liu Shilong , Li Jihao , Wang Shuaida , Hai Zhenyin , Liu Zhichun , Li Junyang
Published: February 2025

High-temperature thin-film thermocouples (TFTCs) have gained significant attention in the aerospace and energy industries due to their compact size and millisecond response time. Although previous studies have reduced the size of TFTCs to the millimeter scale, the heat flow field has continued to limit temperature measurement accuracy. To address this issue, this study used an electrohydrodynamic printing process to fabricate tungsten-rhenium TFTCs with a thickness at the micrometer scale. In the static test, the tungsten-rhenium TFTCs showed good performance with a measurement accuracy better than 1.2%, repeatability better than 0.99%, and a drift rate of 0.72%/h. In dynamic tests, the response time was 1.2 ms. Additionally, during flame gun heating tests, the response time and temperature measurement accuracy exceeded those of the standard thermocouple.
Cavitation Erosion of Protective Coating Based on Cordierite Filler and Epoxy Matrix
Authors: Pavlović Marko , Dojčinović Marina , Nikolić Jasmina , Aleksić Stanko , Tucović Nedeljko , Čeganjac Zoran , Drmanić Saša
Published: February 2025

The goal of this study is to investigate the surface morphology changes induced by the cavitation erosion of a coating based on cordierite with an epoxy matrix for an aluminum substrate. The literature review shows a certain lack of knowledge regarding the coating’s resistance to wearing induced by water flow, which is a highly important property of the material immersed in or in contact with water streams. The main idea behind the investigation is that such a protective coating will also improve the cavitation erosion resistance of metal substrates. The protective coatings were based on cordierite filler (88 wt.%) and epoxy resin (7 wt.%). The filler, made of a mixture of kaolin, alumina, and talc, is obtained by a sintering procedure that took place at 1350 °C. X-ray diffraction analysis and scanning electron microscopy were employed in the characterization of the produced filler. The adherence of the obtained epoxy-based protective coating and resistance to water flow were tested by the ultrasonic vibration method (i.e., cavitation erosion testing). Scanning electron microscopy was used for analysis of the coating’s morphology upon cavitation erosion. Based on the value of the cavitation erosion rate and the analyzed final surface damage, it was assessed that the investigated protective coating is resistant to cavitation erosion.
Mortality-Related Factors and 1-Year Survival in Patients After Intracranial Stenting for Intracranial Arterial Critical Stenosis and Occlusion
Authors: Inanc Yusuf , Polat Esra , Karatas Mesut , Sabanoglu Cengiz , Sahin Kader Eliz , Inanc Ibrahim Halil
Published: February 2025

Background: Studies analyzing factors associated with mortality after intracranial stenting are limited. We aimed to investigate potential factors associated with 1-year mortality after urgent or elective intracranial stenting in those patients with intracranial atherosclerotic stenosis. Methods: Patients, who underwent urgent intracranial stenting of the target lesion either due to acute stroke unresponsive to mechanical thrombectomy, or who underwent elective stenting for symptomatic intracranial atherosclerotic stenosis were included in the study. The Modified Rankin Scale (mRS) score was evaluated on admission and grouped accordingly: ≤2 vs. >2. Restenosis and mortality rates in the 1-year follow-up were also analyzed. Results: A total of 60 patients were included in the study; the mean age was 60.2 (±10.8). The ratio of urgent/elective intracranial stenting was 7/53. Complete revascularization was achieved in all patients, but no periprocedural complications occurred. The rate of in-hospital mortality was 1/60, 1-year mortality due to any cause 4/60, and restenosis in a 1-year follow-up was 4/60. The age over 65 years, previous history of stroke, atrial fibrillation (AF), and rheumatic mitral valve disease were associated with mortality (p < 0.001, p = 0.002, p = 0.017, and p = 0.003, respectively). The median mRS score on admission was lower in the surviving patients at 1 year (p = 0.001). Conclusions: Intracranial stenting may provide long-term survival with low adverse event rates in elective and selected emergency cases. Advanced age, poor functional status, previous stroke, AF, and rheumatic mitral valve disease are associated with 1-year mortality.
Untargeted Lipidomic Biomarkers for Liver Cancer Diagnosis: A Tree-Based Machine Learning Model Enhanced by Explainable Artificial Intelligence
Authors: Colak Cemil , Yagin Fatma Hilal , Algarni Abdulmohsen , Algarni Ali , Al-Hashem Fahaid , Ardigò Luca Paolo
Published: February 2025

Background and Objectives: Liver cancer ranks among the leading causes of cancer-related mortality, necessitating the development of novel diagnostic methods. Deregulated lipid metabolism, a hallmark of hepatocarcinogenesis, offers compelling prospects for biomarker identification. This study aims to employ explainable artificial intelligence (XAI) to identify lipidomic biomarkers for liver cancer and to develop a robust predictive model for early diagnosis. Materials and Methods: This study included 219 patients diagnosed with liver cancer and 219 healthy controls. Serum samples underwent untargeted lipidomic analysis with LC-QTOF-MS. Lipidomic data underwent univariate and multivariate analyses, including fold change (FC), t-tests, PLS-DA, and Elastic Network feature selection, to identify significant biomarker candidate lipids. Machine learning models (AdaBoost, Random Forest, Gradient Boosting) were developed and evaluated utilizing these biomarkers to differentiate liver cancer. The AUC metric was employed to identify the optimal predictive model, whereas SHAP was utilized to achieve interpretability of the model’s predictive decisions. Results: Notable alterations in lipid profiles were observed: decreased sphingomyelins (SM d39:2, SM d41:2) and increased fatty acids (FA 14:1, FA 22:2) and phosphatidylcholines (PC 34:1, PC 32:1). AdaBoost exhibited a superior classification performance, achieving an AUC of 0.875. SHAP identified PC 40:4 as the most efficacious lipid for model predictions. The SM d41:2 and SM d36:3 lipids were specifically associated with an increased risk of low-onset cancer and elevated levels of the PC 40:4 lipid. Conclusions: This study demonstrates that untargeted lipidomics, in conjunction with explainable artificial intelligence (XAI) and machine learning, may effectively identify biomarkers for the early detection of liver cancer. The results suggest that alterations in lipid metabolism are crucial to the progression of liver cancer and provide valuable insights for incorporating lipidomics into precision oncology.
High Strength–Ductility Synergy of As-Cast B2-Containing AlNbTaTiZr Refractory High-Entropy Alloy Under Intermediate and Dynamic Strain Rates
Authors: Naseer Hashim , Wang Yangwei , Khan Muhammad Abubaker , Brechtl Jamieson , Afifi Mohamed A.
Published: February 2025

Understanding the mechanical behavior of materials under various strain-rate regimes is critical for many scientific and engineering applications. Accordingly, this study investigates the strain-rate-dependent compressive mechanical behavior of B2-containing (TiZrNb)79.5(TaAl)20.5 refractory high-entropy alloy (RHEA) at room temperature. The RHEA is prepared by vacuum arc melting and is tested over intermediate (1.0 × 10−1 s−1, 1.0 s−1) and dynamic (1.0 × 103 s−1, 2.0 × 103 s−1, 2.8 × 103 s−1, 3.2 × 103 s−1, and 3.5 × 103 s−1) strain rates. The alloy characterized as hybrid body-centered-cubic (BCC)/B2 nanostructure reveals an exceptional yield strength (YS) of ~1437 MPa and a fracture strain exceeding 90% at an intermediate (1.0 s−1) strain rate. The YS increases to ~1797 MPa under dynamic strain-rate (3.2 × 103 s−1) loadings, which is a ~25 % improvement in strength compared with the deformation at the intermediate strain rate. Microstructural analysis of the deformed specimens reveals the severity of dislocation activity with strain and strain rate that evolves from fine dislocation bands to the formation of localized adiabatic shear bands (ASBs) at the strain rate 3.5 × 103 s−1. Consequently, the RHEA fracture features mixed ductile–brittle morphology. Overall, the RHEA exhibits excellent strength–ductility synergy over a wide strain-rate domain. The study enhances understanding of the strain-rate-dependent mechanical behavior of B2-containing RHEA, which is significant for alloy processes and impact resistance applications.
Epidemiology and Clinical Characteristics of Laboratory-Confirmed COVID-19 and Influenza Infections in Children: A 2015–2024 Study in Taiwan
Authors: Lee Hao-Yuan , Chen Chien-Chin , Ko Shu-Hua , Hsu Yu-Lung , Chang En-Pen , Hsu Yu-Chau , Li Meng-Yen , Chen Chyi-Liang , Lee Wen-Yuan
Published: February 2025

The COVID-19 pandemic and Taiwan’s strict prevention policies from May 2020 to April 2023 significantly altered the epidemiology of viral infections. This study analyzed pediatric COVID-19 and influenza cases at Wei Gong Memorial Hospital from January 2015 to March 2024. Clinical features were compared among children hospitalized during the Omicron BA.2.3.7 (April–July 2022), Omicron BA.5 (August–December 2022), and Omicron JN.1 (2024) waves and those with influenza in 2024 and 2015–2016. Between 2015 and 2024, there were 2729 influenza A (36.6%), 974 influenza B (13.1%), and 3752 COVID-19 (50.3%) cases, with 84.7% of COVID-19 cases occurring in May–December 2022. In 2024, high fever (>40 °C) was more common in influenza A cases (32.9%) than in COVID-19 or influenza B (p < 0.004). Leukocytosis (>12,000/µL) was more frequent in COVID-19 cases (33.3%) than in influenza A (12.2%) or B (0%) (p < 0.001). Pneumonia was more prevalent in COVID-19 cases in 2024 (27.3%) than in 2022 (p ≤ 0.030), and pneumonia rates for influenza A (14.8%) and B (16.7%) in 2024 exceeded those in 2015–2016 (p ≤ 0.030). Increased pneumonia rates in 2024 emphasize the importance of vigilance and timely intervention for pediatric COVID-19 and influenza cases.
Geochemistry and U–Pb Chronology of the Triassic Yanchang Formation in the Southern Ordos Basin, China: Implications for Provenance and Geological Setting
Authors: Luo Fenhong , Gong Hujun , Liu Hang , Lv Bin , Xue Dali
Published: February 2025

During the deposition of the Middle–Upper Triassic Yanchang Formation, the southern margin of the Ordos Basin (OB) serves as a critical area for investigating the tectonic interactions between the North China Block (NCB) and Qinling Orogenic Belt (QOB). The provenance record of this sedimentary succession can be utilized to trace basin–mountain interactions using petrological, geochemical, and zircon age geochronological studies. We analyzed lithic fragments, geochemistry, and detrital zircon U–Pb ages of samples from the Xunyi Sanshuihe field profile, Weibei Uplift. Discrimination diagrams of major and trace elements revealed provenances and tectonic-sedimentary settings. Middle–Upper Triassic sandstones comprise quartz, feldspar, and lithic fragments. Their compositions are plotted within recycled orogenic and magmatic arc provenance fields. Multiple element diagrams reveal a felsic igneous rock provenance. Detrital zircon age spectra display four prominent age groups, which are ca. 240–270, 410–450, 1800–2200, and 2400–2600 Ma, and one minor age group, that is, 870–1197 Ma in the Late Triassic sample. We conclude that the provenance of the Yanchang Formation changed significantly during the Middle–Late Triassic. The Late Triassic sediments were mainly QOB-derived, and the basement was from the NCB. The pre-Triassic strata and Longmen pluton in the southwest of OB were the provenance of Middle Triassic sediments. The QOB suffered rapid uplift and denudation, resulting in rapid deposition and deep-water deposition in the southern OB, which provides excellent conditions for the high-quality oil shale of Ch 7.
Anti-Epstein–Barr Virus Activities of Flavones and Flavonols with Effects on Virus-Related Cancers
Authors: Hassan Sherif T. S.
Published: February 2025

The Epstein–Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors.
Discovery of N-(2-Acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide Derivatives as Novel Potential BCR-ABL1 Inhibitors Through Structure-Based Virtual Screening
Authors: Wang Shuaixing , Wang Minyi , Li Zi , Xu Guofeng , Wang Dayan
Published: February 2025

BCR-ABL1 kinase is a critical driver of chronic myeloid leukemia (CML) pathophysiology. The approval of allosteric inhibitor asciminib brings new hope for overcoming drug resistance caused by mutations in the ATP-binding site. To expand the chemical diversity of BCR-ABL1 kinase inhibitors with positive anti-tumor effect with asciminib, structure-based virtual screening and molecular dynamics simulations were employed to discover novel scaffolds. This approach led to the identification of a series of N-(2-acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide derivatives as new BCR-ABL1 inhibitors. The most potent compound, 10m, demonstrated inhibition of BCR-ABL-dependent signaling and showed an anti-tumor effect against K562 cells, with an IC50 value of 0.98 μM. Compound 10m displayed powerful synergistic anti-proliferation and pro-apoptotic effects when combined with asciminib, highlighting its potential as a promising lead for the development of potential BCR-ABL inhibitors.
In Situ Thermal Decomposition of Potassium Borohydride for Borophene Synthesis and Its Application in a High-Performance Non-Volatile Memory Device
Authors: Tian Qian , Liang Xinchao , Xu Maoping , Liu Yi , Wu Qilong , Tai Guoan
Published: February 2025

Borophene, a revolutionary two-dimensional (2D) material with exceptional electrical, physical, and chemical properties, holds great promise for high-performance, highly integrated information storage systems. However, its metallic nature and structural instability have significantly limited its practical applications. To address these challenges, hydrogenated borophene has emerged as an ideal alternative, offering enhanced stability and semiconducting properties. In this study, we report a novel and scalable method for synthesizing hydrogenated borophene via the in situ thermal decomposition of potassium borohydride in a substrate-free environment. This approach enables the production of borophene with outstanding crystallinity, uniformity, and continuity, representing a significant advancement in borophene fabrication techniques. Furthermore, the hydrogenated borophene-based non-volatile memory device we developed exhibits a high ON/OFF-current ratio exceeding 105, a low operating voltage of 2 V, and excellent long-term cycling stability. These groundbreaking results demonstrate the immense potential of 2D borophene-based materials in next-generation high-performance information storage devices.
Secondary-Structure-Informed RNA Inverse Design via Relational Graph Neural Networks
Authors: Manzourolajdad Amirhossein , Mohebbi Mohammad
Published: February 2025

RNA inverse design is an essential part of many RNA therapeutic strategies. To date, there have been great advances in computationally driven RNA design. The current machine learning approaches can predict the sequence of an RNA given its 3D structure with acceptable accuracy and at tremendous speed. The design and engineering of RNA regulators such as riboswitches, however, is often more difficult, partly due to their inherent conformational switching abilities. Although recent state-of-the-art models do incorporate information about the multiple structures that a sequence can fold into, there is great room for improvement in modeling structural switching. In this work, a relational geometric graph neural network is proposed that explicitly incorporates alternative structures to predict an RNA sequence. Converting the RNA structure into a geometric graph, the proposed model uses edge types to distinguish between the primary structure, secondary structure, and spatial positioning of the nucleotides in representing structures. The results show higher native sequence recovery rates over those of gRNAde across different test sets (eg. 72% vs. 66%) and a benchmark from the literature (60% vs. 57%). Secondary-structure edge types had a more significant impact on the sequence recovery than the spatial edge types as defined in this work. Overall, these results suggest the need for more complex and case-specific characterization of RNA for successful inverse design.
Independent Predictors of Circulating Trimethylamine N-Oxide (TMAO) and Resistin Levels in Subjects with Obesity: Associations with Carotid Intima-Media Thickness and Metabolic Parameters
Authors: Pescari Denisa , Mihuta Monica Simina , Bena Andreea , Stoian Dana
Published: February 2025

Background: Obesity contributes to cardiometabolic risk, including subclinical atherosclerosis and insulin resistance. This study examines the predictive roles of trimethylamine N-oxide (TMAO) and resistin in relation to carotid intima-media thickness and metabolic parameters; Methods: Sixty adults (18–71 years) with varying body weights were assessed for body composition, subclinical atherosclerosis, and blood biomarkers, including TMAO and resistin; Results: TMAO correlated strongly with CIMT (r = 0.674, p < 0.001), indicating its role in subclinical atherosclerosis. Logistic regression identified TMAO (threshold 380; AUC = 0.880, accuracy = 91.7%) as a predictor of cardiometabolic risk. Resistin was associated with CIMT, WHR, and total cholesterol, inversely linked to LDL cholesterol (p = 0.003). Less active participants exhibited higher TMAO (p = 0.001) and resistin (p = 0.02). Family histories of obesity and diabetes correlated with elevated TMAO, while resistin linked to shorter sleep duration and diabetes history, highlighting their importance in obesity-related cardiometabolic risks; Conclusions: TMAO is strongly linked to abdominal fat, insulin resistance, and subclinical atherosclerosis, while resistin is associated with lipid metabolism and aging. Their combined assessment enhances the prediction of obesity-related cardiometabolic risk, supporting their role in risk stratification and targeted interventions.
The Sunshine Paradox: Unraveling Risk Factors for Low Vitamin D Status Among Non-Pregnant Women in Lebanon
Authors: El-Mallah Carla , Yarparvar Amirhossein , Galetti Valeria , Obeid Omar , Boutros Mira , Safadi Gloria , ZeinEddine Razan , Ezzeddine Nour El Hoda , Kouzeiha Maya , Kobayter Diana , Wirth James P. , Abi Zeid Daou Mirella , Asfahani Farah , Hilal Nadeen , Hamadeh Randa , Abiad Firass , Petry Nicolai
Published: February 2025

Background/Objectives: Vitamin D—crucial for bone health, immune function, and hormone regulation—is deficient worldwide, affecting around half the population, particularly women. The study aims to determine the prevalence and risk factors of vitamin D deficiency and hypovitaminosis D in non-pregnant women in Lebanon. Methods: A national cross-sectional survey sampled households across Lebanon, covering 2803 non-pregnant women aged 15 to 49. Demographic information and dietary habits were collected, and anthropometric measurements and serum analyses, including 25-hydroxyvitamin D (25(OH)D) concentrations, were conducted. Multivariable Poisson regressions were constructed to calculate the adjusted prevalence ratio (aPR) for vitamin D deficiency and hypovitaminosis D of variables. Results: The prevalence of vitamin D deficiency (<30 nmol/L) among non-pregnant women in Lebanon was 37.9%, while 69.2% had hypovitaminosis D (<50 nmol/L). Wearing a veil (hijab) was identified as the most significant risk factor for both vitamin D deficiency (aPR = 3.76) and hypovitaminosis D (aPR = 1.47). Additionally, olive skin and dark skin were both associated with an increased prevalence of vitamin D deficiency (olive skin: aPR = 1.14; dark skin: aPR = 1.28), while only dark skin color was associated with hypovitaminosis D (aPR = 1.10). In contrast, protective factors against vitamin D deficiency and hypovitaminosis D included daily sun exposure exceeding one hour (aPR = 0.83–0.91) and vitamin D supplementation (aPR = 0.30–0.55). Anemia, folate deficiency, and vitamin B12 deficiency were significantly associated with a higher prevalence of vitamin D deficiency, hypovitaminosis D, or both. BMI was not significantly associated with vitamin D deficiency; however, women with underweight (aPR = 1.13) and obesity (aPR = 1.12) exhibited a higher prevalence of hypovitaminosis D. Conclusions: Vitamin D deficiency and hypovitaminosis D affect a significant portion of non-pregnant women in Lebanon, with veiling (hijab wearing), limited sun exposure, and lack of supplementation as primary risk factors. Future work should focus on tailoring recommendations for vitamin D supplementation, sun exposure, and food fortification to effectively address the diverse risk factors in the population.
Mandragora autumnalis Distribution, Phytochemical Characteristics, and Pharmacological Bioactivities
Authors: Albahri Ghosoon , Badran Adnan , Baki Zaher Abdel , Alame Mohamad , Hijazi Akram , Daou Anis , Mesmar Joelle Edward , Baydoun Elias
Published: February 2025

In the Mediterranean and Himalayan regions, the genus Mandragora (family Solanaceae), sometimes called mandrake, is widely utilized in herbal therapy and is well-known for its mythical associations. Objective: To compile up-to-date information on M. autumnalis’s therapeutic properties. Its pharmacological properties and phytochemical composition are particularly covered in managing several illnesses, including diabetes, cancer, and heart disease. Methods: Articles on the review topic were found by searching major scientific literature databases, such as PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, and Medicinal and Aromatic Plants Abstracts. Additionally, general online searches were conducted using Google Scholar and Google. The time frame for the search included items released from 1986 to 2023. Results:Mandragora has been shown to contain a variety of phytochemicals, including coumarins, withanolides, and alkaloids. The pharmacological characteristics of M. autumnalis, such as increasing macrophage anti-inflammatory activity, free radicals inhibition, bacterial and fungal growth inhibition, cytotoxic anticancer activities in vivo and in vitro against cancer cell lines, and enzyme-inhibitory properties, are attributed to these phytochemicals. Furthermore, M. autumnalis also inhibits cholinesterase, tyrosinase, α-amylase, α-glucosidase, and free radicals. On the other hand, metabolic risk factors, including the inhibition of diabetes-causing enzymes and obesity, have been treated using dried ripe berries. Conclusions: Investigations into the pharmacological and phytochemical characteristics of M. autumnalis have revealed that this plant is a rich reservoir of new bioactive substances. This review aims to provide insight into the botanical and ecological characteristics of Mandragora autumnalis, including a summary of its phytochemical components and antioxidant, antimicrobial, antidiabetic, anticancer, enzyme-inhibitory properties, as well as toxicological implications, where its low cytotoxic activity against the normal VERO cell line has been shown. More research on this plant is necessary to ensure its efficacy and safety. Still, it is also necessary to understand the molecular mechanism of action behind the observed effects to clarify its therapeutic potential.
Fractures Associated with Immune Checkpoint Inhibitors: A Disproportionality Analysis of the World Health Organization Pharmacovigilance Database
Authors: Koseki Takenao , Hamano Hirofumi , Hatano Masakazu , Tobe Takao , Ieda Ryo , Nakai Tsuyoshi , Zamami Yoshito , Yamada Shigeki
Published: February 2025

Background/Objectives: The risk of fractures associated with immune checkpoint inhibitors (ICIs) is increasing; however, the relationship between fracture risk and potential factors, such as osteoporosis and hyperthyroidism, remains unclear. Methods: Using VigiBase, the World Health Organization’s global pharmacovigilance database, we investigated the signals for osteoporosis, hyperthyroidism, and fractures associated with ICIs (nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, and tremelimumab) by calculating information components (ICs) and their 95% confidence intervals (CIs). Furthermore, we estimated the association between the occurrence of fractures in patients receiving ICIs and osteoporosis or hyperthyroidism. Results: Signals of hyperthyroidism (IC = 4.66, 95% CI: 4.58–4.73), but not osteoporosis (IC = −1.79, 95% CI: −2.22 to −1.36) or fractures (IC = −0.21, 95% CI: −0.36 to −0.06), were detected in patients using ICIs. Osteoporosis (odds ratio: 118.00, 95% CI: 61.00–230.00) was associated with an increased reporting frequency of fractures related to ICIs, whereas hyperthyroidism (odds ratio: 0.60, 95% CI: 0.19–1.87) was not associated with such an increase. Conclusions: The VigiBase analysis indicates that the use of ICIs does not increase the reporting frequency of osteoporosis or fractures. Additionally, hyperthyroidism did not increase the reporting frequency of fractures associated with ICIs.
Probing nS/nD Rydberg States via 6P3/2 Intermediate Level Using Electromagnetically Induced Transparency in 87Rb
Authors: Li Donghao , Xu Beining , Qin Keyu , Jia Xin , Zhao Changtao , Zhou Yaoting , Xu Zhongxiao
Published: February 2025

We perform precise measurements of the 87Rb Rydberg excitation spectrum by using electromagnetically induced transparency (EIT) in a ladder system. We utilize a two-photon excitation configuration with the probe and control lasers at 420 nm and 1013 nm, respectively. In this work, we employ 6P3/2,F′ = 3 as an intermediate state to excite the high-lying Rydberg states of the nS and nD series, with principal quantum numbers ranging from n=35 to n=70. To improve the signal-to-noise ratio (SNR) in this inverted level scheme (λp<λc), we apply a 100 kHz chopping to the control beam, which is followed by a demodulation operated with a lock-in amplifier. Additionally, we verify the ionization energies and determine the quantum defects for the nS and nD series, respectively. Our work offers a database for applications of large-scale quantum simulation and quantum computation with the 87Rb atom array.
Genome-Wide Identification Analysis of the 4-Coumarate: Coa Ligase (4CL) Gene Family in Brassica U’s Triangle Species and Its Potential Role in the Accumulation of Flavonoids in Brassica napus L.
Authors: Zhang Mengzhen , Tian Mengjiao , Weng Ziwuyun , Yang Yaping , Pan Nian , Shen Shulin , Zhao Huiyan , Du Hai , Qu Cunmin , Yin Nengwen
Published: February 2025

4-Coumarate: CoA ligase (4CL) is a key branch point enzyme at the end of the phenylpropanoid metabolic pathway. It regulates the synthesis of various metabolites and participates in plant growth and development by catalyzing the formation of CoA ester compounds. However, 4CL family members have not been identified and analyzed among U’s triangle species in Brassica. In this study, 53 4CL genes were identified in Brassica U’s triangle species and divided into 4 groups (group I, II, III and IV) according to phylogenetic relationship. Based on phylogenetics, gene structure, conserved motifs, chromosome localization and collinearity analysis, 4CLs were relatively conserved in the evolution of Brassica U’s triangle species. The promoter region contains a large number of cis-acting elements, implying the functional diversity of 4CLs. Further combining transcriptome data and reverse transcription quantitative PCR (RT-qPCR), we found that Bna4CLs have tissue specificity and can not only respond to exogenous phytohormone changes but also regulate the flavonoid biosynthetic pathway in the yellow- and black-seeded B. napus. Our results complement the lack of research on the 4CL gene family in Brassica, clarify the sequence characteristics and functional diversity of these genes and lay a foundation for further exploration of 4CL genes in response to abiotic stress and regulation of seed coat flavonoid accumulation.
Study on Flowering Dynamics and Pollination Habits of Monochasma savatieri Under Artificial Cultivation Conditions
Authors: Zhang Haoqian , Wang Qiuling , Wei Jianhe
Published: February 2025

The research aimed to investigate the reproductive biology of M. Savatieri (Monochasma savatieri Franch. ex Maxim.), focusing on its floral structure, developmental stages, flowering dynamics, pollen dispersal characteristics, stigma development, and longevity, as well as self-crossing affinity in both indoor and outdoor cultivation conditions. The study divided the flower development process into four distinct stages: the bud stage (1–3 days), the present bud stage (4–8 days), the pollination stage (9–14 days), and the fruiting stage (15–35 days). Pollen dispersal begins one hour after flowering during the pollination stage and ends within five hours under both indoor and outdoor sunny conditions. Pollen remains highly viable for up to 60 days. Stigma receptivity reaches its maximum at 94.44% on the first day of flowering, decreases to 68.2% by the fourth day, and further declines to 16.7% on the fifth day. The plant, with an outcrossing index (OCI) of 3, shows a 28.80% outcrossing rate in indoor environments and 9.57% in outdoor conditions. It primarily relies on heterogamous pollination while being capable of both self-pollination and artificial pollination. The results provide significant insights into the breeding and production of M. savatieri.
Design and Development of Carbon–Silicon-Based Air Purification Filters with Antibacterial Properties
Authors: Mutushev Alibek , Kaya Ayla , Tulepov Marat , Kudyarova Zhanar , Baiseitov Dauren , Mukhanov Dauren
Published: February 2025

The article presents the results of developing carbon-silicon sorbents that demonstrate high efficiency in capturing various types of dust particles, along with partial antibacterial activity. Dust particles ranging from 0.65 to 150 microns were effectively retained by the sorbent, with organic dust capture efficiency varying between 74% and 98%, making these sorbents suitable for air purification in highly polluted indoor environments. The antibacterial activity was tested on Bacillus paramycoides and Pseudomonas koreensis strains using the diffusion method on a solid nutrient medium. Testing showed that sorbent samples with different concentrations of the active ingredient exhibited varying degrees of bacterial growth suppression, with Sample No. 2 demonstrating the highest activity. Optimizing the sorbent composition and increasing the concentration of active components may enhance its antibacterial properties. These sorbents hold great potential for use in air purification systems with additional protection against bacterial contamination, making them promising for environments with high standards for air hygiene and cleanliness.
MoonLIGHT and MPAc: The European Space Agency’s Next-Generation Lunar Laser Retroreflector for NASA’s CLPS/PRISM1A (CP-11) Mission
Authors: Muccino Marco , Montanari Michele , Lauretani Rudi , Remujo Castro Alejandro , Rubino Laura , Denni Ubaldo , Rodriquez Raffaele , Salvatori Lorenzo , Tibuzzi Mattia , Filomena Luciana , Mauro Lorenza , Currie Douglas , Bargiacchi Giada , Battista Emmanuele , Capozziello Salvatore , Maiello Mauro , Porcelli Luca , Delle Monache Giovanni , Dell’Agnello Simone
Published: February 2025

Since 1969, 55 years ago, Lunar Laser Ranging (LLR) has provided accurate and precise (down to ~1 cm RMS) measurements of the Moon’s orbit thanks to the Apollo and Lunokhod Cube Corner Retroreflector (CCR) Laser Retroreflector Arrays (LRAs) deployed on the Moon. Nowadays, the current level of precision of these measurements is largely limited by the lunar librations affecting the old generation of LRAs. To improve this situation, next-generation libration-free retroreflectors are necessary. To this end, the Satellite/lunar/GNSS laser ranging/altimetry and cube/microsat Characterization Facilities Laboratory (SCF_Lab) at the Istituto Nazionale di Fisica Nucleare—Laboratori Nazionali di Frascati (INFN-LNF), in collaboration with the University of Maryland (UMD) and supported by the Italian Space Agency (ASI), developed MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), a single large CCR with a front face diameter of 100 mm, nominally unaffected by librations, and with optical performances comparable to the Apollo/Lunokhod LRAs of CCRs. Such a big CCR (hereafter, ML100) is mounted into a specifically devised, designed, and manufactured robotic actuator, funded by the European Space Agency (ESA), the so-called MoonLIGHT Pointing Actuator (MPAc), which, once its host craft has landed on the Moon, will finely align the front face of the ML100 towards the Earth. The (optical) performances of such a piece of hardware, MoonLIGHT+MPAc, were tested in/by the SCF_Lab in order to ensure that it was space flight ready before its integration onto the deck of the host craft. After its successful deployment on the Moon, additional and better-quality LLR data (down to ~ 1 mm RMS or better for the contribution of the laser retroreflector instrument, MoonLIGHT, to the total LLR error budget) will be available to the community for future and enhanced tests of gravitational theories.