bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative and Quantitative Analyses of Automotive Exhaust Plumes for Remote Emission Sensing Application Using Gas Schlieren Imaging Sensor System
Authors: Imtiaz Hafiz Hashim , Schaffer Paul , Liu Yingjie , Hesse Paul , Bergmann Alexander , Kupper Martin
Published: August 2024

Remote emission sensing (RES) is a state-of-the-art technique for monitoring thousands of vehicles on the road every day to detect high emitters. Modern commercial RES systems use absorption spectroscopy to measure the ratio of pollutants to CO2 from vehicle exhaust gases. In this work, we present an approach to enable direct concentration measurements by spectroscopic techniques in RES through measurement of the absorption path length. Our gas schlieren imaging sensor (GSIS) system operates on the principle of background-oriented schlieren (BOS) imaging in combination with advanced image processing and deep learning techniques to calculate detected exhaust plume sizes. We performed a qualitative as well as a quantitative analysis of vehicle exhaust and plume dimensions with the GSIS system. We present the system details and results from the GSIS system in the lab in comparison to a BOS model based on flow simulations, the results from characterization measurements in the lab with defined gas mixtures and temperatures, and the results from measurements on the road from different vehicles.
An Exploration of Ideals and Filters in Triangle Algebras
Authors: Noumen Euclide , Tchoua Yinga Fabrice , Koguep Njionou Blaise Blériot , Cornelis Chris
Published: August 2024

In the study of algebraic structures related to logical systems, ideals and filters have different meanings and are algebraic notions related to logical provable formulas. Unlike the classical Boolean lattice theory, ideals and filters are not dual notions in residuated lattices. An interesting subclass of residuated lattices is the class of triangle algebras, which is an equational representation of interval-valued residuated lattices that provides an algebraic framework for using closed intervals as truth values in fuzzy logic. The main aim of this article is to introduce and study the concept of ideals in triangle algebras and investigate the connection between ideals and filters. We first point out that the construction procedure for the filter generated by a subset of a triangle algebra established by another study is incorrect, and we proceed to give an alternative characterization.
Extreme Behavior of Competing Risks with Random Sample Size
Authors: Bai Long , Hu Kaihao , Wen Conghua , Tan Zhongquan , Ling Chengxiu
Published: August 2024

The advances in science and technology have led to vast amounts of complex and heterogeneous data from multiple sources of random sample length. This paper aims to investigate the extreme behavior of competing risks with random sample sizes. Two accelerated mixed types of stable distributions are obtained as the extreme limit laws of random sampling competing risks under linear and power normalizations, respectively. The theoretical findings are well illustrated by typical examples and numerical studies. The developed methodology and models provide new insights into modeling complex data across numerous fields.
Limit Property of an L2-Normalized Solution for an L2-Subcritical Kirchhoff-Type Equation with a Variable Exponent
Authors: Zhu Xincai , Wu Hanxiao
Published: August 2024

This paper is concerned with the following L2-subcritical Kirchhoff-type equation −a+b∫R2|∇u|2dxsΔu+V(x)u=μu+β|u|2u,x∈R2, with ∫R2|u|2dx=1. We give a detailed analysis of the limit property of the L2-normalized solution when exponent s tends toward 0 from the right (i.e., s↘0). Our research extends previous works, in which the authors have displayed the limit behavior of L2-normalized solutions when s=1 as a↘0 or b↘0.
Anion Intercalation/De-Intercalation Mechanism Enabling High Energy and Power Densities of Lithium-Ion Capacitors
Authors: Zhang Yang , Lao Junquan , Xiao Ping
Published: August 2024

The growing demands for electrochemical energy storage systems is driving the exploration of novel devices, with lithium-ion capacitors (LICs) emerging as a promising strategy to achieve both high energy density and fast charge capability. However, the low capacitance of commercial activated carbon (AC) cathode based on anion absorption/desorption limits LIC applications. Herein, commercial graphite is proposed as the cathode to construct an innovative AC (−)//graphite (+) system. The graphite cathode functions as anion hosting, allowing reversible intercalation/de-intercalation of anions into/from its interlayers. The as-designed AC (−)//graphite (+) full cell achieves stable cycling with 90.6% capacity retention after 200 cycles at 0.1 A g−1 and a prolonged lifespan with 87.5% capacity retention after 5000 cycles at 0.5 A g−1 with the upper cut-off voltage of 5.0 V, yielding a high average Coulombic efficiency (CE) of 99.3%. Moreover, the full cell exhibits a high energy density (>200 Wh kg−1) and power density of 7.7 kW kg−1 (calculated based on active mass in both electrodes). These performances exceed most LICs based on anions absorption/desorption on the surface of AC cathodes. This work explores an effective electrode revolution with the assistance of anion intercalation/de-intercalation chemistry for developing novel LICs with high energy and power densities.
Calcium-Enhanced Medium-Based Delivery of Splice Modulating Antisense Oligonucleotides in 2D and 3D hiPSC-Derived Neuronal Models
Authors: Buijsen Ronald A. M. , van der Graaf Linda M. , Kuijper Elsa C. , Pepers Barry A. , Daoutsali Elena , Weel Lotte , Raz Vered , Parfitt David A. , van Roon-Mom Willeke M. C.
Published: August 2024

Antisense technology demonstrates significant potential for addressing inherited brain diseases, with over a dozen products already available and numerous others in the development pipeline. The versatility of differentiating induced pluripotent stem cells (iPSCs) into nearly all neural cell types proves invaluable for comprehending the mechanisms behind neurological diseases, replicating cellular phenotypes, and advancing the testing and development of new therapies, including antisense oligonucleotide therapeutics. While delivering antisense oligonucleotides (ASOs) to human iPSC-based neuronal models has posed challenges, this study explores various delivery methods, including lipid-based transfection, gymnotic uptake, Ca(2+)-enhanced medium (CEM)-based delivery, and electroporation, in 2D and 3D hiPSC-derived neuronal models. This study reveals that CEM-based delivery exhibits efficiency and low toxicity in both 2D neuronal cultures and 3D brain organoids. Furthermore, the findings indicate that CEM is slightly more effective in neurons than in astrocytes, suggesting promising avenues for further exploration and optimization of preclinical ASO strategies in the treatment of neurological disorders.
Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment
Authors: Peracaula Miriam , Sebastian Laura , Francisco Iria , Vilaplana Marc Bonnin , Rodríguez-Chiaradía Diego A. , Tura-Ceide Olga
Published: August 2024

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE.
Uncovering the Contrasts and Connections in PASC: Viral Load and Cytokine Signatures in Acute COVID-19 versus Post-Acute Sequelae of SARS-CoV-2 (PASC)
Authors: Compeer Brandon , Neijzen Tobias R. , van Lelyveld Steven F. L. , Martina Byron E. E. , Russell Colin A. , Goeijenbier Marco
Published: August 2024

The recent global COVID-19 pandemic has had a profound and enduring impact, resulting in substantial loss of life. The scientific community has responded unprecedentedly by investigating various aspects of the crisis, particularly focusing on the acute phase of COVID-19. The roles of the viral load, cytokines, and chemokines during the acute phase and in the context of patients who experienced enduring symptoms upon infection, so called Post-Acute Sequelae of COVID-19 or PASC, have been studied extensively. Here, in this review, we offer a virologist’s perspective on PASC, highlighting the dynamics of SARS-CoV-2 viral loads, cytokines, and chemokines in different organs of patients across the full clinical spectrum of acute-phase disease. We underline that the probability of severe or critical disease progression correlates with increased viral load levels detected in the upper respiratory tract (URT), lower respiratory tract (LRT), and plasma. Acute-phase viremia is a clear, although not unambiguous, predictor of PASC development. Moreover, both the quantity and diversity of functions of cytokines and chemokines increase with acute-phase disease severity. Specific cytokines remain or become elevated in the PASC phase, although the driving factor of ongoing inflammation found in patients with PASC remains to be investigated. The key findings highlighted in this review contribute to a further understanding of PASC and their differences and overlap with acute disease.
Comparative Efficacy and Safety of Weekly GLP-1/GIP Agonists vs. Weekly Insulin in Type 2 Diabetes: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Ayesh Hazem , Suhail Sajida , Ayesh Suhail , Niswender Kevin
Published: August 2024

Background: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. Objectives: This study compares the efficacy and tolerability of once-weekly insulin analogs (icodec and BIF) with once-weekly GLP-1/GIP agonists (semaglutide, exenatide, tirzepatide, dulaglutide) in managing type 2 diabetes mellitus (T2DM). Methods: We conducted a network meta-analysis (NMA) using data from randomized controlled trials (RCTs) that compared these treatments with a baseline of daily basal insulin. Primary outcomes included changes in HbA1c, body weight, and tolerability. Results: The analysis integrated data from 25 RCTs, involving 18,257 patients. Tirzepatide significantly outperformed other treatments in reducing HbA1c and promoting weight loss. Weekly insulins, compared to GLP-1/GIP agonists, showed a more tolerable profile and were beneficial for certain patient demographics emphasizing weight stability. Conclusion: Our findings suggest that while once-weekly GLP-1/GIP agonists provide superior glycemic control and weight management, weekly insulins offer viable options for patients prioritizing fewer side effects and weight stability. This comprehensive comparison aids in refining personalized treatment strategies for T2DM management.
Scanning Electron Microscopy (SEM) Evaluation of the Ultrastructural Effects on Conjunctival Epithelial Cells of a New Multiple-Action Artificial Tear Containing Cross-Linked Hyaluronic Acid, Cationic Liposomes and Trehalose
Authors: Troisi Mario , Del Prete Salvatore , Troisi Salvatore , Marasco Daniela , Rinaldi Michele , Costagliola Ciro
Published: August 2024

The authors performed an ex vivo and in vivo evaluation of the ultrastructural effects on the conjunctival epithelial cells of a new multiple-action tear substitute containing cross-linked hyaluronic acid, lipids and trehalose (Trimix®), using scanning electron microscopy (SEM) with conjunctival impression cytology. The ex vivo study highlights the persistence and distribution of the product at 5 and 60 min on a monolayer of conjunctival epithelial cells and an increase in microvilli density at the 60 min evaluation. In vivo examination was conducted on three subjects with different grades of ocular surface inflammation, treated with one drop of the product twice daily for thirty days. At the baseline (T0) and twelve hours after the last administration of the tear drop (T30), impression cytology of the upper bulbar conjunctiva for SEM evaluation of conjunctival epithelial cells was carried out. Slit lamp examination (SLE), corneal and conjunctival Fluotest, tear film break-up time (TBUT), and ocular surface disease index (OSDI) questionnaires were also performed to correlate the ultrastructural results with the clinical findings. After 30 days of treatment, a significant improvement in all clinical and symptomatic parameters and in the condition of the ocular surface was detected, with microvillar regeneration and strengthening in all the patients, and a complete restoration in 2/3 of them. The persistence and distribution of the product on the epithelial cells was also noted 12 h after the last administration. The results, therefore, suggest a marked epitheliotropic effect along with a high residence time of the tear substitute.
Development and Evaluation of Fucoidan-Loaded Electrospun Polyvinyl Alcohol/Levan Nanofibers for Wound Dressing Applications
Authors: Ismayilova Natavan , Zia Muhammad Khaqan , Akkaya Hatice Selen , Ulag Songul , Guldorum Yeliz , Oner Ebru Toksoy , Ince Erol , Duta Liviu , Gunduz Oguzhan
Published: August 2024

Wound dressing is an ancient technique for promoting healing, and modern technology has led to the development of advanced dressings that enhance patient care. Nanofiber-based wound dressings are a medical innovation with enhanced properties, including improved adhesion, reduced infection rates, and increased tissue regeneration. This article focuses on electrospun nanofibrous wound dressing materials produced using the widely adopted method of electrospinning. This article explores several parameters that influence fiber size, including electrical conductivity, electric potential, collector distance, viscosity, flow rate, and surface tension. With Fucoidan (FUC) loading, an increase in the fiber diameter of the control group from 310 nm to 395 nm was observed. This research also examines the use of Halomonas Levan (HL), a polysaccharide, and polyvinyl alcohol (PVA) polymer as wound dressing materials to enhance the mechanical properties of the latter. The incorporation of various concentrations of FUC into PVA-HL electrospun nanofibers yielded diverse effects on tensile strength: an enhancement was observed in the PVA-HL-10FUC formulation, while reductions were noted in the PVA-HL-13FUC and PVA-HL-15FUC formulations. The WST1 assay demonstrated that none of the samples exhibited cytotoxicity up to 72 h, as cell viability increased over time. In conclusion, nanofibrous PVA-HL structures loaded with FUC, which promote tissue regeneration and prevent infection, could be considered a novel wound dressing material.
A Finger-Actuated Sample-Dosing Capillary-Driven Microfluidic Device for Loop-Mediated Isothermal Amplification
Authors: Le Xuan , Chan Jianxiong , McMahon James , Wisniewski Jessica A. , Coldham Anna , Alan Tuncay , Kwan Patrick
Published: August 2024

Loop-mediated isothermal amplification (LAMP) has attracted significant attention for rapid and accurate point-of-care diagnostics. However, integrating sample introduction, lysis, amplification, and detection steps into an easy-to-use, disposable system has so far been challenging. This has limited the uptake of the technique in practical applications. In this study, we developed a colourimetric one-step LAMP assay that combines thermolysis and LAMP reaction, to detect the SARS-CoV-2 virus in nasopharyngeal swab samples from COVID-19-infected individuals. The limit of detection was 500 copies per reaction at 65 °C for 25 min in reaction tubes. Additionally, we developed a finger-operated capillary-driven microfluidic device with selective PVA coating. This finger-actuated microfluidic device could self-dose the required sample amount for the LAMP reaction and inhibit sample evaporation. Finally, we integrated the LAMP assay into the microfluidic device by short-term pre-storage of the LAMP master mix. Using this device, nasopharyngeal swab samples from COVID-19-infected individuals showed positive results at a reaction time of 35 min at 65 °C. This integrated device may be adapted to detect other RNA viruses of interest rapidly.
Investigation of the Innovative Combined Reuse of Phosphate Mine Waste Rock and Phosphate Washing Sludge to Produce Eco-Friendly Bricks
Authors: Inabi Omar , Khalil Abdessamad , Zouine Abir , Hakkou Rachid , Benzaazoua Mostafa , Taha Yassine
Published: August 2024

Phosphate mining generates substantial quantities of waste rock during the extraction of sedimentary ores, leading to significant environmental concerns as these wastes accumulate around mining sites. The industry is under increasing pressure to adopt more sustainable practices, necessitating considerable financial investments in remediation and technological advancements. Addressing these challenges requires a holistic strategy that balances social responsibility, environmental preservation, and economic viability. This study proposes an innovative, cost-effective, and environmentally friendly method to manufacture compressed stabilized earth bricks by combining the valorization of phosphate waste rock (PWR) and phosphate washing sludge (PWS). These bricks offer numerous advantages, including low embodied energy, robust mechanical performance, and excellent insulation and thermal properties. Initially, a Toxicity Characteristic Leaching Procedure (TCLP) test and radiometric surface contamination measurement, carried out on raw materials (PWR and PWS), showed that the results were below the permissible limits. Then, the chemical, mineralogical, and geotechnical properties of the raw materials were characterized. Subsequently, various mixtures were formulated in the laboratory using PWR and PWS, with and without cement as a stabilizer. Optimal formulations were identified and scaled up for pilot production of solid bricks with dimensions of 250 × 125 × 75 mm3. The resulting bricks exhibited thermal conductivity and water absorption coefficients that satisfied standard requirements. This method not only addresses the environmental issues associated with phosphate mining waste but also provides a sustainable solution for building materials production.
Automatic Generation of Standard Nursing Unit Floor Plan in General Hospital Based on Stable Diffusion
Authors: Han Zhuo , Chen Yongquan
Published: August 2024

This study focuses on the automatic generation of architectural floor plans for standard nursing units in general hospitals based on Stable Diffusion. It aims at assisting architects in efficiently generating a variety of preliminary plan preview schemes and enhancing the efficiency of the pre-planning stage of medical buildings. It includes dataset processing, model training, model testing and generation. It enables the generation of well-organized, clear, and readable functional block floor plans with strong generalization capabilities by inputting the boundaries of the nursing unit’s floor plan. Quantitative analysis demonstrated that 82% of the generated samples met the evaluation criteria for standard nursing units. Additionally, a comparative experiment was conducted using the same dataset to train a deep learning model based on Generative Adversarial Networks (GANs). The conclusion describes the strengths and limitations of the methodology, pointing out directions for improvement by future studies.
Study on Axial Fatigue Performance and Life Prediction of High-Strength Bolts at Low Temperatures
Authors: Zhang Liang , Wang Guoqing , Ji Xuanzhe , Zhang Shujia , Lei Honggang
Published: August 2024

High-strength bolts are widely used in outdoor steel structures such as transmission towers and bridges, where they not only endure cyclic wind loads and vehicle loads but also frequently operate in low-temperature environments. However, there is limited research on the axial fatigue performance of high-strength bolts, particularly regarding their mechanical behavior at low temperatures. Therefore, this study conducted a series of fatigue tests on high-strength bolts at 20 °C and 0 °C, both with and without pretension. We established S-N curves and fatigue limits for the three scenarios, revealing that pretension significantly enhances the fatigue life of the bolts, with a 10% increase in fatigue limit at 0 °C compared to 20 °C. However, due to the influence of pretension, the external load has a minimal effect on the actual stress experienced by the bolts, resulting in S-N curves for bolts with pretension being very similar to those for bolts without pretension during cyclic loading. Additionally, we obtained the load–displacement curves and corresponding stiffness degradation patterns of the bolts at both temperatures, finding that all bolts exhibited significant stiffness degradation after reaching 0.8 times their fatigue life. The high-strength bolts at 0 °C demonstrated greater stiffness and faster crack propagation rates, with increases of approximately 6% and 8%, respectively. Furthermore, electron microscope scans were used to clarify the fatigue crack initiation and the evolution of fatigue striations at both temperatures. Finally, by combining refined numerical simulations with the local stress–strain method, the effectiveness of the local stress–strain method for evaluating the fatigue life of bolts without pretension was validated. Building on this, we extended the method to bolts at 0 °C and those subjected to pretension, recommending notch sizes of 0.4 mm and 1.1 mm for fatigue life assessment of bolts with pretension at 0 °C and 20 °C, respectively.
Experimental Investigation on Pure Torsion Behavior of Concrete Beams Reinforced with Glass Fiber-Reinforced Polymer Bars
Authors: Bai Haoyang , Jiang Jiafei , Xue Weichen , Hu Xiang
Published: August 2024

The failure mechanism of torsional concrete beams with fiber-reinforced polymer (FRP) bars is essential for developing the design method. However, limited experimental research has been conducted on the torsion behavior of concrete beams with FRP bars. Therefore, the pure torsion test of four large-scale FRP-RC beams (2800 mm × 400 mm × 200 mm) was conducted to investigate the influence of the stirrup ratio (0, 0.49%, and 0.98%) and longitudinal reinforcement ratio (3.01%, 4.25%) on torsion behavior. The test results indicated that three typical failure patterns, including concrete cracking failure, stirrup rupturing failure, and concrete crushing failure, were observed in specimens without stirrups (stirrup ratio 0), partially over-reinforced specimens (stirrup ratio 0.49%), and over-reinforced specimens (stirrup ratio 0.98%), respectively. The tangent angle of spiral cracks at the midpoint of the long side of the cross-section was approximately 45° initially for all specimens. The torque–twist angle curves exhibited a linear and bilinear behavior for specimens without stirrups and specimens with stirrups, respectively. As the stirrup ratio increased from 0 to 0.98%, torsion capacity increased from 24.9 kN∙m to 27.8 kN∙m, increased by 12%, ultimate twist angle increased from 0.0018 rad/m to 0.0403 rad/m. As the longitudinal reinforcement ratio increased from 3.01% to 4.25%, the torsion capacity increased from 27.8 kN∙m to 28.3 kN∙m, and the ultimate twist angle decreased from 0.0403 rad/m to 0.0244 rad/m. Based on test results, the stirrup strain limit of 5200 με and spiral crack angle of 45° was suggested for torsion capacity calculation. In addition, based on the database of torsion tests, the performance of torsion capacity provisions was assessed.
Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer
Authors: Papadaki Maria A. , Papadaki Eleni , Chatziavraam Sofia , Aggouraki Despoina , Michaelidou Kleita , Fotsitzoudis Charalampos , Vassilakopoulou Maria , Mavroudis Dimitrios , Agelaki Sofia
Published: August 2024

The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC.
Circulating Multiple Myeloma Cells (CMMCs) as Prognostic and Predictive Markers in Multiple Myeloma and Smouldering MM Patients
Authors: Vigliotta Ilaria , Solli Vincenza , Armuzzi Silvia , Martello Marina , Poletti Andrea , Taurisano Barbara , Pistis Ignazia , Mazzocchetti Gaia , Borsi Enrica , Pantani Lucia , Marzocchi Giulia , Testoni Nicoletta , Zamagni Elena , Terracciano Mario , Tononi Paola , Garonzi Marianna , Ferrarini Alberto , Manaresi Nicolò , Cavo Michele , Terragna Carolina
Published: August 2024

In recent years, liquid biopsy has emerged as a promising alternative to the bone marrow (BM) examination, since it is a minimally invasive technique allowing serial monitoring. Circulating multiple myeloma cells (CMMCs) enumerated using CELLSEARCH® were correlated with patients’ prognosis and measured under treatment to assess their role in monitoring disease dynamics. Forty-four MM and seven smouldering MM (SMM) patients were studied. The CMMC medians at diagnosis were 349 (1 to 39,940) and 327 (range 22–2463) for MM and SMM, respectively. In the MM patients, the CMMC count was correlated with serum albumin, calcium, β2-microglobulin, and monoclonal components (p < 0.04). Under therapy, the CMMCs were consistently detectable in 15/40 patients (coMMstant = 1) and were undetectable or decreasing in 25/40 patients (coMMstant = 0). High-quality response rates were lower in the coMMstant = 1 group (p = 0.04), with a 7.8-fold higher risk of death (p = 0.039), suggesting that continuous CMMC release is correlated with poor responses. In four MM patients, a single-cell DNA sequencing analysis on residual CMMCs confirmed the genomic pattern of the aberrations observed in the BM samples, also highlighting the presence of emerging clones. The CMMC kinetics during treatment were used to separate the patients into two subgroups based on the coMMstant index, with different responses and survival probabilities, providing evidence that CMMC persistence is associated with a poor disease course.
Risk Factors for Positive Resection Margins in Breast-Conserving Surgery for Breast Cancer—Retrospective Analysis
Authors: Georgescu Rares , Tutuianu Flavian , Bauer Orsolya , Toganel Anca , Benedek Zalan , Darii Eugeniu , Turdean Sabin , Tutuianu Radoi Cristina
Published: August 2024

The primary objective of this study was to identify preoperative factors that could be associated with positive resection margins. We also tried to analyze the local recurrence and overall survival in patients who received conservative treatment for early-stage breast cancer and correlate these parameters with preoperative factors. A retrospective examination was conducted on the medical records and pathological reports of 143 patients who underwent breast-conserving surgery (BCS) for breast cancer in our department from 2009 to 2017. Postoperative outcomes were assessed through phone contact and statistical analyses, including GraphPad Prism, and Fisher’s exact test, the Chi-square test, and the log-rank test were employed. The results revealed positive resection margins in 7.69% (11 cases) of the 143 patients, with an overall mortality rate of 16.66% for those with positive margins and 6.59% for those with negative margins. Statistical analysis indicated no significant differences in the overall (p = 0.5) or specific (p = 0.53) survival between the positive and negative margin groups. The positive margins were significantly associated with neoadjuvant chemotherapy (p < 0.0001) and the presence of ductal carcinoma in situ (DCIS) (p = 0.01). Among the analyzed factors, two out of sixteen were significantly linked to positive resection margins in BCS, emphasizing their importance in surgical management planning for early-stage breast cancer.
Prognostic Factors in Patients Diagnosed with Gallbladder Cancer over a Period of 20 Years: A Cohort Study
Authors: Toussi Nima , Daida Krishna , Moser Michael , Le Duc , Hagel Kimberly , Kanthan Rani , Shaw John , Zaidi Adnan , Chalchal Haji , Ahmed Shahid
Published: August 2024

Background: Gallbladder cancer (GBC) is an uncommon cancer. This study aimed to determine the outcomes of GBC in relation to geographic, demographic, and clinical factors in a Canadian province from 2000 to 2019. Methods: This population-based retrospective cohort study included all patients diagnosed with gallbladder cancer (GBC) in Saskatchewan, Canada, from 2000 to 2019. Cox proportional multivariate regression analysis was conducted to identify factors associated with poorer outcomes. Results: In total, 331 patients with a median age of 74 years and male–female ratio of 1:2 were identified. Of these patients, 305 (92%) had a pathological diagnosis of GBC. Among patients with documented staging data, 64% had stage IV disease. A total of 217 (66%) patients were rural residents, and 149 (45%) were referred to a cancer center. The multivariate analysis for patients with stage I–III GBC showed that stage III disease [hazard ratio (HR), 2.63; 95% confidence interval (CI), 1.09–6.34)] and urban residence (HR, 2.20; 95% CI, 1.1–4.39) were correlated with inferior disease-free survival. For all patients, stage IV disease (HR, 3.02; 95% CI, 1.85–4.94), no referral to a cancer center (HR, 2.64; 95% CI, 1.51–4.62), lack of surgery (HR, 1.63; 95% CI, 1.03–2.57), a neutrophil–lymphocyte ratio of >3.2 (HR, 1.57; 1.05–2.36), and age of ≥70 years (HR, 1.51; 95% CI, 1.04–2.19) were correlated with inferior overall survival. Conclusions: In this real-world context, the majority of patients with GBC were diagnosed at a late stage and were not referred to a cancer center. For those with early-stage GBC, living in an urban area and having stage III disease were linked to worse outcomes. Across all stages of GBC, stage IV disease, older age, absence of surgery, lack of referral to a cancer center, and a high neutrophil-to-lymphocyte ratio were associated with poorer survival.
The Effects of Radiotherapy on the Sequence and Eligibility of Breast Reconstruction: Current Evidence and Controversy
Authors: Campbell Andrew R. , Didier Alexander J. , Sheikh Taha M. , Ansari Sami , Watkins Dean E. , Fahoury Alan M. , Nandwani Swamroop V. , Rashid Mohammad
Published: August 2024

Immediate breast reconstruction (IBR) following a mastectomy, combined with radiotherapy, presents a multifaceted approach to breast cancer treatment, balancing oncological safety and aesthetic outcomes. IBR, typically involving the use of implants or autologous tissue, aims to restore breast morphology directly after a mastectomy, minimizing the psychological and physical impacts. However, integrating radiotherapy with IBR is complex due to the potential adverse effects on reconstructed tissues. Radiotherapy, essential for reducing local recurrence, can induce fibrosis, capsular contracture, and compromised aesthetic results. This narrative review covers the current trends in the sequencing of breast reconstruction and radiotherapy. We discuss patient selection, timing of radiotherapy, and reconstructive techniques, with special attention paid to quality-of-life outcomes that are increasingly reported in clinical trials. Emerging evidence supports the feasibility of IBR with careful patient selection and tailored therapeutic approaches, although ongoing research is necessary to refine protocols and enhance outcomes. Overall, IBR in the context of radiotherapy remains a promising but intricate treatment modality, requiring a nuanced balance between cancer control and aesthetic restoration.
Sulfamoylated Estradiol Analogs Targeting the Actin and Microtubule Cytoskeletons Demonstrate Anti-Cancer Properties In Vitro and In Ovo
Authors: Mercier Anne Elisabeth , Joubert Anna Margaretha , Prudent Renaud , Viallet Jean , Desroches-Castan Agnes , De Koning Leanne , Mabeta Peace , Helena Jolene , Pepper Michael Sean , Lafanechère Laurence
Published: August 2024

The microtubule-disrupting agent 2-methoxyestradiol (2-ME) displays anti-tumor and anti-angiogenic properties, but its clinical development is halted due to poor pharmacokinetics. We therefore designed two 2-ME analogs in silico—an ESE-15-one and an ESE-16 one—with improved pharmacological properties. We investigated the effects of these compounds on the cytoskeleton in vitro, and their anti-angiogenic and anti-metastatic properties in ovo. Time-lapse fluorescent microscopy revealed that sub-lethal doses of the compounds disrupted microtubule dynamics. Phalloidin fluorescent staining of treated cervical (HeLa), metastatic breast (MDA-MB-231) cancer, and human umbilical vein endothelial cells (HUVECs) displayed thickened, stabilized actin stress fibers after 2 h, which rearranged into a peripheral radial pattern by 24 h. Cofilin phosphorylation and phosphorylated ezrin/radixin/moesin complexes appeared to regulate this actin response. These signaling pathways overlap with anti-angiogenic, extra-cellular communication and adhesion pathways. Sub-lethal concentrations of the compounds retarded both cellular migration and invasion. Anti-angiogenic and extra-cellular matrix signaling was evident with TIMP2 and P-VEGF receptor-2 upregulation. ESE-15-one and ESE-16 exhibited anti-tumor and anti-metastatic properties in vivo, using the chick chorioallantoic membrane assay. In conclusion, the sulfamoylated 2-ME analogs displayed promising anti-tumor, anti-metastatic, and anti-angiogenic properties. Future studies will assess the compounds for myeloproliferative effects, as seen in clinical applications of other drugs in this class.
Agent-Based Modeling of Virtual Tumors Reveals the Critical Influence of Microenvironmental Complexity on Immunotherapy Efficacy
Authors: Wang Yixuan , Bergman Daniel R. , Trujillo Erica , Fernald Anthony A. , Li Lie , Pearson Alexander T. , Sweis Randy F. , Jackson Trachette L.
Published: August 2024

Since the introduction of the first immune checkpoint inhibitor (ICI), immunotherapy has changed the landscape of molecular therapeutics for cancers. However, ICIs do not work equally well on all cancers and for all patients. There has been a growing interest in using mathematical and computational models to optimize clinical responses. Ordinary differential equations (ODEs) have been widely used for mechanistic modeling in immuno-oncology and immunotherapy. They allow rapid simulations of temporal changes in the cellular and molecular populations involved. Nonetheless, ODEs cannot describe the spatial structure in the tumor microenvironment or quantify the influence of spatially-dependent characteristics of tumor-immune dynamics. For these reasons, agent-based models (ABMs) have gained popularity because they can model more detailed phenotypic and spatial heterogeneity that better reflect the complexity seen in vivo. In the context of anti-PD-1 ICIs, we compare treatment outcomes simulated from an ODE model and an ABM to show the importance of including spatial components in computational models of cancer immunotherapy. We consider tumor cells of high and low antigenicity and two distinct cytotoxic T lymphocyte (CTL) killing mechanisms. The preferred mechanism differs based on the antigenicity of tumor cells. Our ABM reveals varied phenotypic shifts within the tumor and spatial organization of tumor and CTLs despite similarities in key immune parameters, initial simulation conditions, and early temporal trajectories of the cell populations.
Inflammatory Bowel Disease and Colorectal Cancer
Authors: Fanizza Jacopo , Bencardino Sarah , Allocca Mariangela , Furfaro Federica , Zilli Alessandra , Parigi Tommaso Lorenzo , Fiorino Gionata , Peyrin-Biroulet Laurent , Danese Silvio , D’Amico Ferdinando
Published: August 2024

Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn’s disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.
Fifty Years of Research in Environmental Photocatalysis: Scientific Advances, Discoveries, and New Perspectives
Authors: Guillard Chantal , Robert Didier
Published: August 2024

The concept of “photocatalysis” was discovered at the beginning of the twentieth century, and research in this area has especially intensified over the past 50 years [...]
The Expression of Toll-like Receptors in Cartilage Endplate Cells: A Role of Toll-like Receptor 2 in Pro-Inflammatory and Pro-Catabolic Gene Expression
Authors: Mengis Tamara , Bernhard Laura , Nüesch Andrea , Heggli Irina , Herger Nick , Devan Jan , Marcus Roy , Laux Christoph J. , Brunner Florian , Farshad Mazda , Distler Oliver , Le Maitre Christine L. , Dudli Stefan
Published: August 2024

Introduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. Methods: Gene expression of TLR1–10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. Results: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. Conclusions: The expression of TLR1–10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC.
Centriole Translational Planar Polarity in Monociliated Epithelia
Authors: Donati Antoine , Schneider-Maunoury Sylvie , Vesque Christine
Published: August 2024

Ciliated epithelia are widespread in animals and play crucial roles in many developmental and physiological processes. Epithelia composed of multi-ciliated cells allow for directional fluid flow in the trachea, oviduct and brain cavities. Monociliated epithelia play crucial roles in vertebrate embryos, from the establishment of left–right asymmetry to the control of axis curvature via cerebrospinal flow motility in zebrafish. Cilia also have a central role in the motility and feeding of free-swimming larvae in a variety of marine organisms. These diverse functions rely on the coordinated orientation (rotational polarity) and asymmetric localization (translational polarity) of cilia and of their centriole-derived basal bodies across the epithelium, both being forms of planar cell polarity (PCP). Here, we review our current knowledge on the mechanisms of the translational polarity of basal bodies in vertebrate monociliated epithelia from the molecule to the whole organism. We highlight the importance of live imaging for understanding the dynamics of centriole polarization. We review the roles of core PCP pathways and of apicobasal polarity proteins, such as Par3, whose central function in this process has been recently uncovered. Finally, we emphasize the importance of the coordination between polarity proteins, the cytoskeleton and the basal body itself in this highly dynamic process.
The Complement System Is Essential for Arteriogenesis by Enhancing Sterile Inflammation as a Relevant Step in Collateral Artery Growth
Authors: Zhu Amanda , Baur Carolin , Götz Philipp , Elbs Katharina , Lasch Manuel , Faro Anna , Preissner Klaus T. , Deindl Elisabeth
Published: August 2024

Arteriogenesis is an inflammatory driven mechanism, describing the growth of a natural bypass from pre-existing collateral arteries to compensate for an occluded artery. The complement system component C3 is a potent natural inflammatory activator. Here, we investigated its impact on the process of collateral artery growth using C3-deficient (C3 −/−) and wildtype control mice in a murine hindlimb model of arteriogenesis. Induction of arteriogenesis by unilateral femoral artery ligation resulted in decreased perfusion recovery in C3 −/− mice on day 7 as shown by Laser Doppler imaging. Immunofluorescence staining revealed a reduced vascular cell proliferation in C3 −/− mice. Gene expression analysis displayed a significant reduction in monocyte chemoattractant protein-1 (MCP-1) expression in C3 −/− mice. Interestingly, 3 days after induction of arteriogenesis, the number of macrophages (CD68+) recruited to growing collaterals was not affected by C3 deficiency. However, a significant reduction in inflammatory M1-like polarized macrophages (CD68+/MRC1−) was noted. Forced mast cell activation by Compound 48/80 as well as exogenous MCP-1 application rescued the number of M1-like polarized macrophages along with perfusion recovery in C3 −/− mice. In summary, this study demonstrates that complement C3 influences arteriogenesis by mediating MCP-1 expression, which is essential for the induction and enhancement of sterile inflammation.
Comparing Viral Vectors and Fate Mapping Approaches for Astrocyte-to-Neuron Reprogramming in the Injured Mouse Cerebral Cortex
Authors: Puglisi Matteo , Lao Chu Lan , Wani Gulzar , Masserdotti Giacomo , Bocchi Riccardo , Götz Magdalena
Published: August 2024

Direct neuronal reprogramming is a promising approach to replace neurons lost due to disease via the conversion of endogenous glia reacting to brain injury into neurons. However, it is essential to demonstrate that the newly generated neurons originate from glial cells and/or show that they are not pre-existing endogenous neurons. Here, we use controls for both requirements while comparing two viral vector systems (Mo-MLVs and AAVs) for the expression of the same neurogenic factor, the phosphorylation-resistant form of Neurogenin2. Our results show that Mo-MLVs targeting proliferating glial cells after traumatic brain injury reliably convert astrocytes into neurons, as assessed by genetic fate mapping of astrocytes. Conversely, expressing the same neurogenic factor in a flexed AAV system results in artefactual labelling of endogenous neurons fatemapped by birthdating in development that are negative for the genetic fate mapping marker induced in astrocytes. These results are further corroborated by chronic live in vivo imaging. Taken together, the phosphorylation-resistant form of Neurogenin2 is more efficient in reprogramming reactive glia into neurons than its wildtype counterpart in vivo using retroviral vectors (Mo-MLVs) targeting proliferating glia. Conversely, AAV-mediated expression generates artefacts and is not sufficient to achieve fate conversion.