bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Progress on the Mechanism and Application of the Type I CRISPR-Cas System
Authors: Yang Peihong , Zhang Shuai , Hu Debao , Li Xin , Guo Yiwen , Guo Hong , Zhang Linlin , Ding Xiangbin
Published: November 2024

The CRISPR-Cas system functions as an adaptive immune mechanism in archaea and bacteria, providing defense against the invasion of foreign nucleic acids. Most CRISPR-Cas systems are classified into class 1 or class 2, with further subdivision into several subtypes. The primary distinction between class 1 and class 2 systems lies in the assembly of their effector modules. In class 1 systems, the effector complex consists of multiple proteins with distinct functions, whereas in class 2 systems, the effector is associated with a single protein. Class 1 systems account for approximately 90% of the CRISPR-Cas repertoire and are categorized into three types (type I, type IV, and type III) and 12 subtypes. To date, various CRISPR-Cas systems have been widely employed in the field of genetic engineering as essential tools and techniques for genome editing. Type I CRISPR-Cas systems remain a valuable resource for developing sophisticated application tools. This review provides a comprehensive review of the characteristics, mechanisms of action, and applications of class 1 type I CRISPR-Cas systems, as well as transposon-associated systems, offering effective approaches and insights for future research on the mechanisms of action, as well as the subsequent development and application of type I CRISPR-Cas systems.
The Cooper-Pair Distribution Function of Untwisted-Misaligned Bilayer Graphene
Authors: Camargo-Martínez Jose Alfredo , González-Pedreros Guillermo Iván , Mesa Fredy
Published: November 2024

The Cooper-pair distribution function Dcp(ω,Tc) of Untwisted-Misaligned Bilayer Graphene (UMBLG) in the presence of an external electric field is calculated and analysed within the framework of first-principle calculations. A bilayer graphene structure is proposed using a structural geometric approximation, enabling the simulation of a structure rotated at a small angle, avoiding a supercell calculation. The Dcp(ω,Tc) function of UMBLG indicates the presence of the superconducting state for specific structural configurations, which is consistent with the superconductivity in Twisted Bilayer Graphene (TBLG) reported in the literature. The Dcp(ω,Tc) function of UMBLG suggests that Cooper-pairs are possible in the low-frequency vibration region. Furthermore, the structural geometric approximation allowed the evaluation of the effect of the electric field on the superconducting state of UMBLG and its superconducting critical temperature through the Ncp parameter.
Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression?
Authors: Zhang Xiaolan , Liu Lingbo
Published: November 2024

Malignant tumors can evade immune surveillance and elimination through multiple mechanisms, with the induction of immune cell dysfunction serving as a crucial strategy. Mounting evidence indicates that T cell senescence constitutes the primary mechanism underlying T cell dysfunction in acute myeloid leukemia (AML) and represents one of the potential causes of immunotherapy failure. AML usually progresses rapidly and is highly susceptible to drug resistance, thereby resulting in recurrence and patient mortality. Hence, disrupting the immune interface within the bone marrow microenvironment of AML has emerged as a critical objective for synergistically enhancing tumor immunotherapy. In this review, we summarize the general characteristics, distinctive phenotypes, and regulatory signaling networks of senescent T cells and highlight their potential clinical significance in the bone marrow microenvironment of AML. Additionally, we discuss potential therapeutic strategies for alleviating and reversing T cell senescence.
Renal Epithelial Complement C3 Expression Affects Kidney Fibrosis Progression
Authors: Stepanova Ganna , Manzéger Anna , Mózes Miklós M. , Kökény Gábor
Published: November 2024

Kidney fibrosis is a hallmark of chronic kidney diseases. Evidence shows that genetic variability and complement component 3 (C3) might influence tubulointerstitial fibrosis. Still, the role of renal C3 production in the epithelial-to-mesenchymal transition (EMT) and genetically determined fibrosis progression remains undiscovered. The kidneys of fibrosis-resistant C57Bl/6J (B6) and fibrosis-prone CBA/J (CBA) and BALB/cJ (BalbC) mice (n = 4–8/group) were subjected to unilateral ureteral obstruction (UUO) and analyzed after 1, 3, and 7 days, along with human focal glomerular sclerotic (FSGS) and healthy kidneys. Mouse primary tubular epithelial cells (PTECs) were investigated after 24 h of treatment with transforming growth factor β (TGFβ) or complement anaphylatoxin 3a (C3a) agonist (n = 4/group). UUO resulted in delayed kidney injury in fibrosis-resistant B6 mice, but very early renal C3 messenger RNA (mRNA) induction in fibrosis-prone CBA and BalbC mice, along with collagen I (Col1a1) and collagen III (Col3a1). CBA depicted the fastest fibrosis progression with the highest C3, lipocalin-2 (Lcn2), Tgfb1, and chemokine (C-C motif) ligand 2 (Ccl2) expression. Human FSGS kidneys depicted C3 mRNA over-expression and strong tubular C3 immunostaining. In PTECs, C3a agonist treatment induced pro-fibrotic early growth response protein 1 (EGR1) expression and the EMT, independent of TGFβ signaling. We conclude that de novo renal tubular C3 synthesis is associated with the genetically determined kidney fibrosis progression rate in mice and the pathogenesis of FSGS in humans. This tubular C3 overproduction can, through local pro-fibrotic effects, influence the progression of chronic kidney disease.
Molecular Composition and Kinetics of B Cells During Ibrutinib Treatment in Patients with Chronic Lymphocytic Leukemia
Authors: Veyhe Sólja Remisdóttir , Cédile Oriane , Dahlmann Sara Kamuk , Krejcik Jakub , Abildgaard Niels , Høyer Thor , Møller Michael Boe , Thomassen Mads , Juul-Jensen Karen , Frederiksen Henrik , Dybkær Karen , Hansen Marcus Høy , Nyvold Charlotte Guldborg
Published: November 2024

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells due to constitutive B-cell receptor (BCR) signaling, leading to apoptosis resistance and increased proliferation. This study evaluates the effects of the Bruton Tyrosine Kinase (BTK) inhibitor ibrutinib on the molecular composition, clonality, and kinetics of B cells during treatment in CLL patients. Employing a multi-omics approach of up to 3.2 years of follow-up, we analyzed data from 24 CLL patients, specifically focusing on nine patients treated with ibrutinib monotherapy. In this study, clonal stability was observed within the ibrutinib-treated group following an effective initial clinical response, where clonotype frequencies of residual CLL cells remained high and stable, ranging from 74.9% at 1.5 years to 87.7% at approximately 3 years. In contrast, patients treated with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax exhibited substantial reductions in clonal frequencies, approaching molecular eradication. Deep whole-exome sequencing revealed minimal genomic progression in the ibrutinib group, maintaining somatic drivers and variant allele frequencies (VAF) above 0.2 throughout treatment. At the single-cell level, the NF-κB pathway inhibition and apoptotic signals were detected or even augmented during treatment in ibrutinib-treated patients. These findings may corroborate the role of ibrutinib in stabilizing the genomic landscape of CLL cells, preventing significant genomic evolution despite maintaining a high clonal burden within the residual B-cell compartment.
Morphometric, Biomechanical and Histologic Assessment of Physiologic Ovine Cervical Intervertebral Disc: An Experimental Study and Brief Literature Review
Authors: Gkantsinikoudis Nikolaos , Koltsakidis Savvas , Prodromou Panagiotis , Aggelidou Eleni , Kapetanakis Stylianos , Tsiridis Eleftherios , Magras Ioannis , Psalla Dimitra , Kazakos George , Tzetzis Dimitrios , Kritis Aristeidis
Published: November 2024

The ovine cervical spine model has been established as a representative model of the human cervical spine in the current literature, and is the most commonly used large animal model in studies investigating pathogenesis and treatment strategies for intervertebral disc (IVD) degeneration. However, existing data regarding morphometry, biomechanical profiles and the microscopic features of a physiological ovine cervical IVD remain scarce. Hence, the aim of this study was to perform a multimodal morphometric, biomechanical and histologic evaluation of a normal ovine cervical IVD. For this purpose, nine ovine cervical IVDs were harvested from three female sheep, and subjected to morphometrical, biomechanical and histologic analyses. The biomechanical assessment included the performance of cyclic compression, creepand compressive strength tests in a controlledlaboratory environment. Histological evaluation was performed using hematoxylin–eosin, Masson’s trichrome and Alcian blue staining. The results from the morphometric analysis showed that the range of disc heights was 4–9 mm in all surfaces, featuring a constant increase from cranial to caudal levels. Biomechanical evaluation revealed that cyclic loading for 20 cycles was necessary for preconditioning so that the repeatability of the force–displacement hysteresis response is present. The critical failure point was defined at 15.5 MPa, whereas Young’s modulus of elasticity was 1.2 MPa. The histologic assessment demonstrated the presence of a concentric arrangement of collagen lamellae in external annulus fibrosus, along with the sparsely organized internal nucleus pulposus. Ovine cervical IVD represents a complex structure with distinct features that should be considered by researchers in this field in order to optimize the reliability and validity of testing results.
Cystic Fibrosis Screening Efficacy and Seasonal Variation in California: 15-Year Comparison of IRT Cutoffs Versus Daily Percentile for First-Tier Testing
Authors: Sciortino Stanley , Graham Steve , Bishop Tracey , Matteson Jamie , Carter Sarah , Wu Cindy H. , Sharma Rajesh
Published: November 2024

The California Genetic Disease Screening Program (GDSP) employs a fixed immunoreactive trypsinogen (IRT) cutoff followed by molecular testing to screen newborns for cystic fibrosis (CF). The cutoffs approximate a 1.6% yearly IRT screen-positive rate; however, seasonal variation in IRT population means has led us to develop a model to establish fixed IRT cutoffs that anticipate seasonal variation and minimize missed cases below cutoff. We utilized an ARIMA model to fit monthly IRT screen-positive percentiles and estimated regular seasonal expectations. We established a retrospective cohort followed for at least 1.5 years to capture missed false-negative CF cases. We compared missed CF cases identified by seasonal cutoffs vs. floating cutoffs. GDSP screened 7,410,003 newborns, from July 2007 to December 2022, and missed 36 CF cases below the fixed cutoff; five of the 36 were within 3 ng/mL below the cutoff. There was a regular, seasonal cycle that varied from 1.4% in summer to 1.8% in winter. We would have missed 59 CF cases using a 1.6% daily floating cutoff. California would need to use a 4% daily floating cutoff to improve our current detection rate, which would double the number of specimens sent for costly molecular analysis.
A Comprehensive Analysis of Early Alzheimer Disease Detection from 3D sMRI Images Using Deep Learning Frameworks
Authors: Abbasian Pouneh , Hammond Tracy A.
Published: November 2024

Accurate diagnosis of Alzheimer’s Disease (AD) has largely focused on its later stages, often overlooking the critical need for early detection of Early Mild Cognitive Impairment (EMCI). Early detection is essential for potentially reducing mortality rates; however, distinguishing EMCI from Normal Cognitive (NC) individuals is challenging due to similarities in their brain patterns. To address this, we have developed a subject-level 3D-CNN architecture enhanced by preprocessing techniques to improve classification accuracy between these groups. Our experiments utilized structural Magnetic Resonance Imaging (sMRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset, specifically the ADNI3 collection. We included 446 subjects from the baseline and year 1 phases, comprising 164 individuals diagnosed with EMCI and 282 individuals with NC. When evaluated using 4-fold stratified cross-validation, our model achieved a validation AUC of 91.5%. On the test set, it attained an accuracy of 81.80% along with a recall of 82.50%, precision of 81.80%, and specificity of 80.50%, effectively distinguishing between the NC and EMCI groups. Additionally, a gradient class activation map was employed to highlight key regions influencing model predictions. In comparative evaluations against pretrained models and existing literature, our approach demonstrated decent performance in early AD detection.
Bt Trait Efficacy Against Corn Earworm, Helicoverpa zea, (Lepidoptera: Noctuidae) for Preserving Grain Yield and Reducing Mycotoxin Contamination of Field Corn
Authors: Barton William Yancey , Buntin George David , Toews Micheal D.
Published: November 2024

The corn earworm, Helicoverpa zea (Boddie), causes persistent ear damage to corn grown in the southeastern United States region. Increased levels of ear damage have been associated with mycotoxin contamination in addition to yield loss. Corn hybrids expressing proteins from the Bacillus thuringiensis (Bt) may provide corn earworm control. A selection of hybrids expressing various Bt traits were evaluated in field experiments across Georgia over two years to assess their efficacy for corn earworm control, grain yield and quality protection, and grain mycotoxin mitigation. Ear damage was significantly reduced only by Bt hybrids expressing the Vip3Aa20 protein. The remaining Bt hybrids expressing Cry proteins provided only marginal control. Ear damage had a variable effect on grain yield and was not correlated with grain aflatoxin contamination. In contrast, grain fumonisin contamination was positively associated with earworm damage. These results indicate Bt hybrids that effectively reduce corn earworm damage may also assist in reducing fumonisin contamination and possibly yield loss.
The Association Between Sarcoidosis and Malignancy: A Comprehensive Population-Based Cohort Study
Authors: Patt Yonatan Shneor , Ben-Shabat Niv , Sharif Kassem , Patt Chen , Elizur Yoav , Arow Mohamad , Cohen Arnon D. , Watad Abdulla , McGonagle Dennis , Amital Howard , David Paula
Published: November 2024

Background: Sarcoidosis is a multisystem granulomatous disorder with a variable clinical course and complications. The relationship between sarcoidosis and malignancies remains unclear, including specific malignancy associations with sarcoidosis and whether the association is short-term, long-term, or a result of misdiagnoses or coincidence. This study investigated the association between sarcoidosis and malignancy by analyzing the varying intervals between the diagnoses of these two conditions to clarify their inter-relationship. Methods: This retrospective cohort study included almost 24,000 sarcoidosis patients and matched controls at a 1:5 ratio in patients diagnosed between 2000 and 2015 in Israel. Patients had a median age of 57 years. Malignancy rates were compared across several timeframes: overall, within one year before or after sarcoidosis diagnosis and more than one year. Logistic regression models were employed to estimate odds ratios for the association between sarcoidosis and malignancy, adjusting for sociodemographic and clinical variables. Results: Sarcoidosis patients had a significantly higher prevalence of malignancies (19.5%) compared to controls (13.6%) (p < 0.001). The association remained significant for both hematologic malignancies (OR: 2.94, 95% CI: 2.41–3.57) and solid malignancies (OR: 1.41, 95% CI: 1.27–1.55). The strongest association was observed with lymphoma, particularly within the first year of sarcoidosis diagnosis (OR: 14.88, 95% CI: 8.83–25.1). Elevated odds for malignancies persisted both within one year and beyond, including sarcoma and soft tissue cancers and genitourinary malignancies. Conclusions: Our study confirms a significant association between sarcoidosis and both hematologic and solid malignancies in both the short and long term across various timeframes. These findings emphasize the need for increased clinical vigilance in sarcoidosis patients and highlight the importance of further research into the shared genetic and environmental mechanisms that may underlie this relationship.
Comparison of Intraocular Pressure Measurements Using Three Different Methods (Goldmann Applanation Tonometry (GAT), Corvis ST, and iCare) Following Penetrating Keratoplasty
Authors: Tziola Tatiana , Tzamalis Argyrios , Koronis Spyridon , Garitsis Panagiotis , Tsinopoulos Ioannis , Ziakas Nikolaos
Published: November 2024

Background/Objectives: Intraocular pressure (IOP) readings using three different methods (Goldmann applanation tonometry (GAT), Corvis ST, and iCare) were compared in patients who underwent penetrating keratoplasty (PK). Methods: An observational cross-sectional study with prospective recruitment of patients was conducted. IOP measurements were acquired using GAT, iCare, and Corvis (including both uncorrected IOP (CVS-IOP) and biomechanical IOP (bIOP)), and the agreement among methods was analyzed using Bland–Altman plots. Secondary outcomes included the influence of CCT, the number of sutures, the size of the corneal donor button, and the use of antiglaucoma topical medications on the IOP readings using the three methods. Results: Twenty-five eyes from 25 patients were included. The Bland–Altman analysis showed the narrowest limits of agreement (LoA) between GAT and bIOP (7.5 mmHg). The difference between iCare and GAT IOP showed a bias of 1.26 ± 3.8 mmHg, with increased variability in cases with more remaining sutures (p = 0.0079). A higher CCT was moderately associated with lower bIOP readings (p = 0.0067), but no significant impact of CCT on the difference in the IOP measurements between GAT and other tonometers was found. Additionally, there were no significant differences in tonometer readings based on the use of antiglaucoma medications or the corneal donor button size. Conclusions: Good agreement was found between iCare, CVS-IOP, bIOP, and GAT-IOP readings with the comparison between GAT-IOP and bIOP resulting in the narrowest 95% LoA. The difference between the GAT-IOP and iCare readings tended to be influenced by the number of sutures at the graft–host interface. Higher CCT values were associated with lower bIOP readings; however, the differences in tonometer readings compared to GAT-IOP were not found to be influenced by CCT.
Periodontal Breakdown, Orthodontic Movements and Pulpal Ischemia Correlations—A Comparison Between Five Study Methods
Authors: Moga Radu-Andrei , Olteanu Cristian Doru , Delean Ada Gabriela
Published: November 2024

Background/Objectives: This study assessed the biomechanical behavior of dental pulp and the neuro-vascular bundle/NVB as well as the ischemic risks during orthodontic movements in a gradual horizontal periodontal breakdown, using five methods and aiming to identify the most accurate one. Methods: Seventy-two models of second lower premolar (from nine patients) were subjected to 3 N of intrusion, extrusion, rotation, tipping, and translation. Five numerical methods, Tresca, Von Mises/VM, Maximum and Minimum Principal, and hydrostatic pressure were used in a total of 1800 numerical simulations. The results were color-coded projections of the stress areas that were then correlated with maximum physiological hydrostatic pressure/MHP and known clinical biomechanical behavior. Results: During periodontal breakdown, all five methods displayed, for all movements, quantitative stresses lower than MHP, suggesting that 3 N are not inducing any local tissular ischemic risks for the healthy intact tissues. All five methods displayed rotation as the most stressful movement during periodontal breakdown, while translation was the least. The NVB was more exposed to ischemic risks than dental pulp during the periodontal breakdown due to constant tissular deformations. Only VM and Tresca methods showed translation as more prone to expose dental pulp (both coronal and radicular) to ischemic risks (than the other movements) during the periodontal breakdown simulation. However, all five methods showed intrusion and extrusion as more prone to expose the NVB to higher ischemic risks than the other movements during the periodontal breakdown simulation. Conclusions: During periodontal breakdown, Tresca and Von Mises were more accurate, with Tresca being the most accurate of all.
Title: Is Celiac Trunk Revascularization Necessary After High-Flow Pancreaticoduodenal Arterial Arcades Aneurysm Retrograde Embolization?
Authors: Jazzar Mohamed Salim , Kobeiter Hicham , Ghosn Mario , Amar Raphael , Zaarour Youssef , Galletto Pregliasco Athena , Desgranges Pascal , Tacher Vania , El Hajjam Mostafa , Derbel Haytham
Published: November 2024

Background and Objective: High-flow pancreaticoduodenal artery (PDA) aneurysms secondary to celiac trunk occlusion or stenosis have a high risk of rupture. Embolization offers a less invasive alternative to surgery. We evaluated the effectiveness and safety of retrograde embolization via the superior mesenteric artery of high-flow PDA aneurysms without celiac trunk revascularization. Methods: This retrospective bicentric study included patients who underwent embolization of high-flow PDA aneurysms due to significant celiac trunk stenosis or occlusion. All patients underwent pre-interventional dynamic contrast-enhanced computed tomography. Retrograde embolization was performed using microcoils and/or liquid agents without celiac trunk revascularization. Follow up involved clinical and radiological assessment at one month. Technical and clinical success were evaluated, and complications were categorized as minor or major. Results: Twenty-three patients (mean age 65 ± 14 years; 52% male) were included. Emergency embolization was required in 12 patients (52%). The technical success rate was 100%. Patients were monitored for a median of 16 months. Clinical success was 87%. No hemorrhagic recurrences were observed. Minor complications occurred in two cases. One major complication involved splenic infarction due to glue migration, requiring splenectomy and intensive unit care admission. Conclusions: Retrograde embolization of high-flow PDA aneurysms is effective and safe without needing celiac trunk revascularization.
Global and Regional Sex-Related Differences, Asymmetry, and Peak Age of Brain Myelination in Healthy Adults
Authors: Khodanovich Marina Y. , Svetlik Mikhail V. , Naumova Anna V. , Usova Anna V. , Pashkevich Valentina Y. , Moshkina Marina V. , Shadrina Maria M. , Kamaeva Daria A. , Obukhovskaya Victoria B. , Kataeva Nadezhda G. , Levina Anastasia Y. , Tumentceva Yana A. , Yarnykh Vasily L.
Published: November 2024

Background: The fundamental question of normal brain myelination in human is still poorly understood. Methods: Age-dependent global, regional, and interhemispheric sex-related differences in brain myelination of 42 (19 men, 23 women) healthy adults (19–67 years) were explored using the MRI method of fast macromolecular fraction (MPF) mapping. Results: Higher brain myelination in males compared to females was found in global white matter (WM), most WM tracts, juxtacortical WM regions, and putamen. The largest differences between men and women, exceeding 4%, were observed bilaterally in the frontal juxtacortical WM; angular, inferior occipital, and cuneus WM; external capsule; and inferior and superior fronto-orbital fasciculi. The majority of hemispheric differences in MPF were common to men and women. Sex-specific interhemispheric differences were found in juxtacortical WM; men more often had left-sided asymmetry, while women had right-sided asymmetry. Most regions of deep gray matter (GM), juxtacortical WM, and WM tracts (except for projection pathways) showed a later peak age of myelination in women compared to men, with a difference of 3.5 years on average. Body mass index (BMI) was associated with higher MPF and later peak age of myelination independent of age and sex. Conclusions: MPF mapping showed high sensitivity to assess sex-related differences in normal brain myelination, providing the basis for using this method in clinics.
The Clinical Usefulness of Evaluating the Lens and Intraocular Lenses Using Optical Coherence Tomography: An Updated Literature Review
Authors: Fernández-Vigo José Ignacio , De-Pablo-Gómez-de-Liaño Lucía , Almorín-Fernández-Vigo Ignacio , De-Pablo-Gómez-de-Liaño Beatriz , Macarro-Merino Ana , García-Feijóo Julián , Fernández-Vigo José Ángel
Published: November 2024

The Lens Dysfunction Syndrome includes two widespread ocular disorders: presbyopia and cataract. Understanding its etiology, onset, progression, impact, prevention, and treatment remains a significant scientific challenge. The lens is a fundamental structure of the ocular dioptric system that allows for focus adjustment or accommodation to view objects at different distances. Its opacification, primarily related to aging, leads to the development of cataracts. Traditionally, lens alterations have been diagnosed using a slit lamp and later with devices based on the Scheimpflug camera. However, both methods have significant limitations. In recent years, optical coherence tomography (OCT) has become a valuable tool for assessing the lens and pseudophakic intraocular lenses (IOLs) in clinical practice, providing a highly detailed non-invasive evaluation of these structures. Its clinical utility has been described in assessing the shape, location or position, and size of the lens, as well as in determining the degree and type of cataract and its various components. Regarding pseudophakic IOLs, OCT allows for the accurate assessment of their position and centering, as well as for detecting possible complications, including the presence of glistening or IOL opacification. Furthermore, OCT enables the evaluation of the posterior capsule and its associated pathologies, including late capsular distension syndrome. This review highlights the key applications of OCT in the assessment of the lens and pseudophakic IOLs.
Real-World Clinical Effectiveness and Safety of Antifibrotics in Progressive Pulmonary Fibrosis Associated with Rheumatoid Arthritis
Authors: Narváez Javier , Aguilar-Coll Martí , Vicens-Zygmunt Vanesa , Alegre Juan José , Bermudo Guadalupe , Molina-Molina María
Published: November 2024

Background/Objectives: Interstitial lung disease (ILD) is one of the most severe complications of rheumatoid arthritis (RA). Real-world data on antifibrotic treatment are needed. Our objective was to evaluate the real-world effectiveness and tolerability of antifibrotic agents in patients with progressive fibrosing RA-ILD. Methods: A longitudinal, retrospective, observational study was conducted on a cohort of RA-ILD patients treated with either nintedanib or pirfenidone. The data collected included pulmonary function test (PFT) results, adverse events (AEs), tolerability, and drug retention. Results: Twenty-seven patients were included; 25 (92.5%) initiated nintedanib, while two initiated pirfenidone. The median follow-up duration was 25 months (IQR 7–27). The mean decline in %pFVC and %pDLCO from ILD diagnosis to the initiation of antifibrotic therapy were −8.9% and −14.8%, respectively. After 6 months of treatment, most patients achieved stabilization in PFT: a ∆%pFVC of +1.2% (p = 0.611 compared with baseline) and a ∆%pDLCO of +3.9% (p = 0.400). Eighteen patients completed one year of therapy, with a modest improvement in %pFVC (+4.7%; p = 0.023) and stabilization in %pDLCO (−3.8%; p = 0.175). This trend persisted among the nine patients who completed 2 years of treatment (%pFVC +7.7%; p = 0.037 and %pDLCO −2.2%; p = 0.621). During the follow-up period, 15% of patients died, and 4% underwent lung transplantation. Adverse events occurred in 81% of patients, leading to discontinuation in 18.5% of cases. The most frequent adverse events were gastrointestinal events and hepatitis, leading to a permanent dose reduction of 40% for nintedanib and 14% for pirfenidone. A second antifibrotic agent was prescribed for 18.5% of the patients. At the end of the follow-up period, 63% of the total cohort remained on antifibrotic therapy. Conclusions: According to our results, antifibrotic initiation was associated with a modest improvement in the trajectory of %pFVC and stabilization in %pDLCO. The discontinuation rate in our cohort (37%) was higher than that reported in clinical trials but similar to that reported in previously published real-world studies.
Interpretation of Historic Urban Landscape Genes: A Case Study of Harbin, China
Authors: Sun Jianqiao , Shao Long
Published: November 2024

The intensifying urbanization has led to the increasing risk of urban landscape character fading away. How to inherit and control the “genes” of urban landscape features is a crucial issue that needs urgent resolution. To address this issue, this study draws on the theory of biological genes, employing methods such as historical information translation, deconstruction and extraction of landscape features, and genetic analysis to establish a research paradigm of “holistic composition interpretation—dynamic evolution interpretation” for historic urban landscape genes. The study applies this paradigm in practice using Harbin, China, as an example. The results indicate that: (1) The historic urban landscape genes are comprised of explicit landscape pattern genes; street and alley texture genes; architectural appearance genes; and implicit human settlement culture genes, industrial culture genes, historical culture genes, and spiritual culture genes. (2) The evolutionary traits of Harbin’s historic urban landscape genes manifest in several ways: the evolution of its landscape pattern genes, featuring “three-tiered terraces, balanced spatial arrangement, surrounded by mountains and rivers, and fan-shaped radial layout”; the evolution of its street and alley texture genes, exhibited through “a blend of Chinese and Western styles, sprawling and interconnected, unit linkage, and multi-dimensional intersections”; the evolution of its architectural style genes, marked by “diverse styles, a harmonious fusion of Chinese and Western elements, grouped interdependence, and adaptation to the times”; the evolution of its human settlement culture genes, highlighted by “a secluded lifestyle, diverse customs, and the coexistence of Chinese and Western cultures”; the evolution of its historical culture genes, distinguished by “unity in diversity and multicultural differentiation”; and the evolution of its spiritual culture genes, characterized by “pluralistic beliefs and inclusiveness”. (3) The essential difference between historic urban landscape genes and other genes lies in their adaptive evolution in response to environmental changes over generations and their ability to reveal the influence mechanisms among genes, between genes and landscape features, and between genes and the environment. The distinction between historic urban landscape genes and other types of genes lies in the adaptive changes that historic urban landscape gene types undergo in response to changes in time and environment. The historic urban landscape gene system itself undergoes adaptive evolution with the urban environment of various historical periods, leading to the emergence and differentiation of new levels. This study can provide new insights into urban heritage conservation, urban landscape management, and rational allocation of urban land use.
Coordination of O-Propyl-N-phenylthiocarbamate to HgI2 and the Crystallographic Characterization of an Anilinium Chloride Thiocarbamate Adduct
Authors: Arar Wafa , Ekici Nuri , Knorr Michael , Jourdain Isabelle , Strohmann Carsten , Kirchhoff Jan-Lukas
Published: November 2024

In order to investigate the coordination chemistry of O-alkyl N-aryl thiocarbamate ligands, HgI2 was reacted with one equivalent of PrOC(=S)N(H)Ph L in toluene solution to afford the 1D polymeric title compound [{IHg(μ-I)}{κ1-PrOC(=S)N(H)Ph}]n CP1. The formation of this iodide-bridged coordination polymer was ascertained by a single-crystal X-ray diffraction study performed at 100 K, as well as the formation of an adduct between anilinium chloride and L forming a supramolecular ribbon of composition [L(PhNH3)(Cl)]. The occurrence of anilinium chloride is due to the partial hydrolysis of L in the presence of HCl.
Structural, Magnetic, and Dielectric Properties of Laser-Ablated CoFe2O4/BaTiO3 Bilayers Deposited over Highly Doped Si(100)
Authors: Oliveira João , Silva Bruna M. , Rebelo Tiago , Rodrigues Pedro V. , Baptista Rosa M. F. , Rodrigues Manuel J. L. F. , Belsley Michael , Lekshmi Neenu , Araújo João P. , Mendes Jorge A. , Deepak Francis Leonard , Almeida Bernardo G.
Published: November 2024

Laser ablation was used to successfully fabricate multiferroic bilayer thin films, composed of BaTiO3 (BTO) and CoFe2O4 (CFO), on highly doped (100) Si substrates. This study investigates the influence of BaTiO3 layer thickness (50–220 nm) on the films’ structural, magnetic, and dielectric properties. The dense, polycrystalline films exhibited a tetragonal BaTiO3 phase and a cubic spinel CoFe2O4 layer. Structural analysis revealed compression of the CoFe2O4 unit cell along the growth direction, while the BaTiO3 layer showed a tetragonal distortion, more pronounced in thinner BTO layers. These strain effects, attributed to the mechanical interaction between both layers, induced strain-dependent wasp-waisted behavior in the films’ magnetic hysteresis cycles. The strain effects gradually relaxed with increasing BaTiO3 thickness. Raman spectroscopy and second harmonic generation studies confirmed BTO’s non-centrosymmetric ferroelectric structure at room temperature. The displayed dielectric permittivity dispersion was modeled using the Havriliak–Negami function combined with a conductivity term. This analysis yielded relaxation times, DC conductivities, and activation energies. The observed BTO relaxation time behavior, indicative of small-polaron transport, changed significantly at the BTO ferroelectric Curie temperature (Tc), presenting activation energies Eτ in the 0.1–0.3 eV range for T < Tc and Eτ > 0.3 eV for T > Tc. The BTO thickness-dependent Tc behavior exhibited critical exponents ν ~ 0.82 consistent with the 3D random Ising universality class, suggesting local disorder and inhomogeneities in the films. This was attributed to the composite structure of BTO grains, comprising an inner bulk-like structure, a gradient strained layer, and a disordered surface layer. DC conductivity analysis indicated that CoFe2O4 conduction primarily occurred through hopping in octahedral sites. These findings provide crucial insights into the dynamic dielectric behavior of multiferroic bilayer thin films at the nanoscale, enhancing their potential for application in emerging Si electronics-compatible magneto-electric technologies.
Modification of Ti-Al-V Alloys with Layers Containing TiN Particles Obtained via the Electrophoretic Deposition Process: Surface and Structural Properties
Authors: Biegun-Żurowska Maria , Berezicka Anna , Gajek Marcin , Goryczka Tomasz , Ziąbka Magdalena
Published: November 2024

The aim of this work was to obtain homogenous coatings containing chitosan with different concentrations of titanium nitride particles (TiN). The coatings were deposited via an electrophoretic process on an etched medically pure Ti-6Al-4V alloy. As part of the study, the zeta potential of the suspensions used for EPD coating deposition was measured, allowing for the optimization of process parameters and the assessment of suspension stability. Subsequently, the research focused on evaluating the microstructure (SEM + EDS), structure (XRD), and surface characteristics (roughness, contact angle, surface energy, microhardness, coating adhesion) of the deposited layers. SEM microscopy confirmed the effective deposition of titanium nitride particles onto the titanium alloy surface. XRD analysis proved the assumed phase composition of the coating. The increase in TiN phase content in the individual layers was confirmed. The chitosan/TiN layer’s introduction altered the alloy surface, increasing its roughness and static water contact angle. The highest roughness and hydrophobic properties were observed in the coating with a 2 wt.% concentration of titanium nitride particles. Additionally, the coating containing the highest concentration of ceramic particles (2 wt.%) exhibited the highest hardness (197 HV) among all the tested layers. However, the TiN particles incorporation in the layer decreased the adhesion strength, from 2.36 MPa (0.5 wt.% TiN) to 1.04 MPa (2 wt.% TiN). The coatings surface and structural properties demonstrate potential as protective layers for implants and are suitable for further biological studies to assess their applicability in medical and veterinary fields.
Fracture Criterion Calibration and Finite Element Simulation in SUS304 Stainless Steel
Authors: Xing Menglong , Liu Yangchao , Lu Jianwei , Huang Xiaomin , Wang Xinge , Xue Jianqi , Zhang Fuming , Du Fengshan
Published: November 2024

In order to calibrate the ductile fracture criterion in SUS304 stainless steel, four tensile samples were designed, their finite element models were established, and uniaxial tensile tests were carried out. The simulation results were compared with the tests. Due to the limitations of finite element software, only a few criteria can be solved in MENTAT of MSC.MARC 2013. In order to make the ductile fracture criteria universal, the HYPELA2 subroutine was used to write the ductile fracture criteria, and the three-point bending simulation was used to verify the ductile fracture criteria program. Finally, the calibration results of different fracture criteria are compared with the test results. The results show that the error between the finite element results of four samples and the test results is small, which verifies the feasibility of the finite element model. Based on the Oh criterion, the correctness of HYPELA2 subroutine development is verified by a three-point bending simulation. In the SH sample, the Freudenthal, C-L, and LeRoy criteria have a better prediction ability, and the prediction error of other criteria is relatively large. All the criteria have a strong prediction ability for the NT20 and CH05 samples.
Development and Road Performance Verification of Aggregate Gradation for Large Stone Asphalt Mixture
Authors: Bi Yufeng , Mu Minghao , Zeng Lujun , Ding Tingting , Qian Chengduo , Yu Deshui , Jiang Yingjun
Published: November 2024

The pavement base and subbase are the main load-bearing structures of asphalt pavement, and their materials need to have sufficient bearing capacity. Therefore, in the development of LSAM-50 mixtures with higher bearing capacity, after significant research and engineering practice, conventional particle size asphalt mixtures have formed their own excellent mineral gradation and have been incorporated into relevant specifications, while LSAM-50 mixtures, including mineral gradation, have not been involved in related research and engineering applications. According to the strength composition mechanism of asphalt mixtures, under the same circumstances of asphalt, due to the large nominal maximum particle size of LSAM-50 and the small amount of asphalt used, the strength of mineral grading is more important than that of asphalt, which is one of the key issues to be solved in the research of LSAM-50 mixtures. This study aims to enhance the road performance of asphalt mixtures with a maximum nominal particle size of 50 mm (LSAM-50). The variation of void ratios in coarse aggregate skeletons was investigated when aggregates of 37.5–53 mm (designated as D1), 19–37.5 mm (designated as D2), and 9.5–19 mm (designated as D3) were mixed in different proportions. Meanwhile, the effects of fine aggregate gradation on the strength of asphalt mortar and the influence of the ratio of coarse to fine aggregates on the mechanical strength of LSAM-50 were examined. A densely graded structure with strong interlocking for LSAM-50 was proposed, and its road performance was verified. The results indicate that when the ratio of D1, D2, and D3 is 5:2:3, the void ratio of the mixed coarse aggregate is minimized. When the decrement factor i is 0.75, the compressive strength and splitting strength of asphalt mortar reach their maxima. Compared with the densely graded asphalt-stabilized aggregate mixture (ATB-30) with a maximum nominal particle size of 37.5 mm, the dynamic stability of LSAM-50 with the proposed gradation is increased by 400%, the low-temperature bending strain by 3%, the SCB bending strength by 47%, and the residual SCB strength by 90%.
Thermal Softening Measurements of Refractory High-Entropy Alloys
Authors: Temesi Ottó K. , Karacs Albert , Chinh Nguyen Q. , Varga Lajos K.
Published: November 2024

Home-built equipment will be presented able to measure the thermal expansion (with a flat indenter) and indentation depth (with a pointed indenter) up to 1100 °C. In dilatometer mode, the allotropic phase transformations can be studied. For hardness, a Rockwell-type measurement is adopted. First, we apply a small load and measure the displacement consisting of a dominant positive thermal expansion and a small negative indentation depth contribution. Then, we repeat the thermal cycle with such a high load that the compensation appears at around 250–300 °C. With increasing temperature, the indentation depth starts to dominate and we can notice a contraction. The indentation depth as a function of temperature, ID(T), will be obtained by subtracting the high load curve from the low load curve. A new rational fraction expression will be tested to describe the thermal softening of pure metals and refractory HEAs. Still, we are working on improving the equipment to extend the working temperature up to 1200 °C.
A Data-Driven-Based Grounding Fault Location Method for the Auxiliary Power Supply System in an Electric Locomotive
Authors: Hou Xinyao , Meng Yang , Ni Qiang
Published: November 2024

Grounding faults are a common type of fault in train auxiliary power supply systems (APS). Timely identification and localization of these faults are crucial for ensuring the stable operation of electric locomotives and the safety of passengers. Therefore, this paper proposes a fault diagnosis method for grounding faults (GFs) that integrates mechanistic insights with data-driven feature extraction. Firstly, this paper analyzes the mechanisms of grounding faults and summarizes the characteristics of their time–frequency distribution. Then, a Short-Time Fourier Transform (STFT) is employed to derive a frequency signature vector enabling classification into three principal categories. Concurrently, a time series sliding window approach is applied to extract time domain indicators for further subdivision of fault types. Finally, a time–frequency hybrid-driven diagnostic model framework is constructed by integrating the frequency distribution with the spatiotemporal map, and validation is conducted using an experimental platform that replicates system fault scenarios with a hardware-in-the-loop (HIL) simulation and executes the real-time diagnostic frameworks on a DSP diagnostic board card. The results demonstrate that the proposed method can detect and accurately locate grounding faults in real time.
Mesoxalate-Bridged Heptanuclear Copper(II) Complexes: Structure and Magnetic Properties
Authors: Gil-Hernández Beatriz , Millan Simon , Gruber Irina , Janiak Christoph , Gómez-García Carlos J. , Sanchiz Joaquín
Published: November 2024

Two new compounds, (NH4)4[Cu7(Hmesox)6(H2O)8]∙10H2O (1) and [Ru(bpy)3]4[Cu7(Hmesox)6Cl2]Cl2∙2CH3CN∙12H2O (2), were prepared and their structures were solved by single-crystal X-ray diffraction (mesoxalic acid = dihydroxypropanedioic acid, H4mesox). The triply deprotonated mesoxalate anion acts as a chelating and bridging ligand with its carboxylate and alkoxide groups, forming the anionic heptanuclear copper(II) clusters [Cu7(Hmesox)6(H2O)8]4− and [Cu7(Hmesox)6Cl2]6− in 1 and 2, respectively. Variable temperature magnetic studies revealed antiferromagnetic interactions in 1 and the coexistence of ferro and antiferromagnetic interactions in 2. The [Ru(bpy)3]2+ cations provided luminescent properties to compound 2.
Solving Nonlinear Equation Systems via a Steffensen-Type Higher-Order Method with Memory
Authors: Wang Shuai , Xian Haomiao , Liu Tao , Shateyi Stanford
Published: November 2024

This article introduces a multi-step solver for sets of nonlinear equations. To achieve this, we consider and develop a multi-step Steffensen-type method without memory, which does not require evaluations of the Fréchet derivatives, and subsequently extend it to a method with memory. The resulting order is 5+2, utilizing the identical number of functional evaluations as the solver without memory, thereby demonstrating a higher computational index of efficiency. Finally, we illustrate the advantages of the proposed scheme with memory through various test problems.
Influence of Nociception Level Monitor (NOL)-Guided Analgesic Delivery on Perioperative Course in Breast Surgeries: A Randomized Controlled Trial
Authors: Malachauskiene Laima , Bhavsar Rajesh , Bakke Skule , Keller Jeppe , Bhavsar Swati , Luy Anne-Marie , Strøm Thomas
Published: November 2024

Background and Objectives: Breast cancer surgeries offer challenges in perioperative pain management, especially in the presence of inherent risk of postoperative nausea and vomiting (PONV) and postmastectomy pain syndrome (PMPS). Inappropriate opioid consumption was speculated as one of the reasons. Through this study, the influence of objective pain monitoring through a nociception level monitor (NOL) on perioperative course in breast surgeries was investigated. Materials and Methods: This was a prospective randomized study conducted at a regional hospital. Sixty female patients posted for breast cancer surgery were randomized equally into study and control groups. Both groups were monitored using BIS and NOL, but in the control group, the NOL monitor was blinded by a cover. Both groups received propofol and remifentanil through target-controlled infusions (TCIs) along with interpectoral, pectoserratus (PECS II), and superficial pectointercostal block. The primary outcome was intraoperative opioid consumption. Secondary outcomes were PONV, eligibility for discharge from the recovery room, and symptoms of PMPS after three months. Results: Two patients were excluded. The study group received significantly less remifentanil (0.9 mg in the study group vs. 1.35 mg in the control group, p = 0.033) and morphine (2.5 mg in study group vs. 5 mg in control group, p = 0.013). There was no difference in PMPS symptoms between the groups. The study group showed longer duration of inadequate analgesia (i.e., 7% vs. 10% of the total intraoperative period in control and study group, respectively, p = 0.008). There was no difference in time to eligibility for discharge from the recovery room between the groups. Conclusions: NOL monitor-guided analgesic delivery reduces intraoperative opioid consumption. No difference was demonstrated on PONV, eligibility for discharge from the recovery room, or PMPS symptoms.