bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the Sysmex XN-V Automated Nucleated Red Blood Cell Enumeration for Canine and Feline EDTA-Anticoagulated Blood
Authors: Ginders Julia , Stirn Martina , Novacco Marilisa , Hofmann-Lehmann Regina , Riond Barbara
Published: January 2024

The enumeration of nRBCs (nucleated red blood cells) by manual counting is time-consuming and imprecise. As the first veterinary hematology analyzer, Sysmex XN-V provides automated nRBC counts. This study aimed to evaluate the performance of Sysmex XN-V in the enumeration of nRBCs for cats and dogs by comparing automated nRBC counts to manual counts from a total of 3810 canine and 2844 feline specimens. Repeatability, reproducibility, stability, carry-over, and linearity were assessed. The repeatability and reproducibility of Sysmex XN-V were good, with mean coefficients of variation (CV) of 4.5% and 5.4%, respectively. Bland–Altman difference analysis revealed mean biases shown as nRBCs/100 WBCs of 0.01 in dogs and 0.11 in cats with low nRBCs (<5/100 WBCs), mean biases of −1.27 in dogs and −0.24 in cats with moderate nRBC counts (5–20 nRBCs/100 WBCs), and mean biases of −7.76 in dogs and −1.31 in cats with high nRBC counts (>20 nRBCs/100 WBCs). The total observable error was below 9% in both species and at all ranges. Overall concordance between methods was high (91% in canine and 93% in feline samples). The automated nRBC count by Sysmex XN-V was found to be accurate and precise and can replace manual counts for cat and dog samples. Non-statistical quality assurance by scattergram evaluation, re-gating, and confirmation by blood smear evaluation is, however, recommended, especially in cases with severe normoblastosis. This advancement will save time, reduce errors, and add prognostic value to hematological results for animal patients.
In Vitro Antibacterial Activity of Microbial Natural Products against Bacterial Pathogens of Veterinary and Zoonotic Relevance
Authors: Barth Stefanie A. , Preussger Daniel , Pietschmann Jana , Feßler Andrea T. , Heller Martin , Herbst Werner , Schnee Christiane , Schwarz Stefan , Kloss Florian , Berens Christian , Menge Christian
Published: January 2024

Antimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations <2 µg/mL against Pasteurella sp. and two of them (CA and CT) also against Mannheimia sp. Those results were confirmed by testing a larger collection of isolates encompassing 64 Pasteurella and 56 Mannheimia field isolates originating from pigs or cattle, which yielded MIC90 values of 0.5, 0.5, and 2 µg/mL against Pasteurella and 0.5, 4, and >16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potential.
Sequential versus Standard Triple Therapy for First-Line Helicobacter pylori Eradication: An Update
Authors: Nyssen Olga P. , Martínez Belén , Mégraud Francis , Savarino Vincenzo , Fallone Carlo A. , Bazzoli Franco , Gisbert Javier P.
Published: January 2024

Background: non-bismuth sequential therapy (SEQ) was suggested as a first-line anti-Helicobacter pylori treatment alternative to standard triple therapy (STT). Methods: We conducted a systematic review with a meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of 10-day SEQ vs. STT (of at least 7 days) using bibliographical searches up to July 2021, including treatment-naïve adult or children. The intention-to-treat (ITT) eradication rate and the risk difference (RD) were calculated. Results: Overall, 69 RCTs were evaluated, including 19,657 patients (9486 in SEQ; 10,171 in STT). Overall, SEQ was significantly more effective than STT (82% vs. 75%; RD 0.08; p < 0.001). The results were highly heterogeneous (I2 = 68%), and 38 studies did not demonstrate differences between therapies. Subgroup analyses suggested that patients with clarithromycin resistance only and all geographical areas but South America could benefit more from SEQ. Both therapies have evolved over the years, showing similar results when STT lasted 14 days; however, a tendency toward lower SEQ efficacy was noted from 2010 onwards. Conclusions: Prior to 2010, SEQ was significantly more effective than STT, notably when 7-day STT was prescribed. A tendency toward lower differences between SEQ and STT has been noted, especially when using 10-day STT. None of the therapies achieved an optimal efficacy and therefore cannot be recommended as a valid first-line H. pylori treatment.
Intraoperative PRO Score Assessment of Actinic Keratosis with FCF Fast Green-Enhanced Ex Vivo Confocal Microscopy
Authors: Hartmann Daniela , Buttgereit Lisa , Stärr Lara , Sattler Elke Christina , French Lars Einar , Deußing Maximilian
Published: January 2024

Actinic keratoses (AKs) represent a common skin cancer in situ associated with chronic sun exposure. Early diagnosis and management of AKs are crucial to prevent their progression to invasive squamous cell carcinoma. Therefore, we investigated AK PRO score assessment using ex vivo confocal laser microscopy (EVCM) coupled with a novel fluorescent dye, FCF Fast Green, to explore its potential for the precise imaging and discrimination of collagen fibers. AK PRO assessment using EVCM demonstrated excellent conformity (95.8%) with histopathologic examination. The additional utilization of FCF Fast Green dye had no impact on AK visualization but showed a high affinity for collagen fibers enabling clear differentiation of collagen alterations between healthy and sun-damaged skin. The enhanced visualization of collagen fiber changes may aid clinicians in accurately identifying AKs and differentiating them from benign skin lesions.
Comparison of the Relative Importance of Factors Affecting the Conveyance of Bulk and Liquid Cargo
Authors: Čižiūnienė Kristina , Matijošius Jonas , Liebuvienė Jūratė , Sokolovskij Edgar
Published: January 2024

The transportation of bulk or liquid cargo is crucial for ensuring the delivery of such cargo to areas lacking well-established infrastructure or favorable natural conditions. These areas may lack sufficient rail or air transport accessibility, or may not have suitable embankments along rivers, lakes or seas with appropriate loading and unloading facilities. Regarding distinctive characteristics, we would like to emphasize the following: (1) Efficient freight accessibility without the need for more infrastructure that is tailored to the existing natural circumstances; (2) An efficient and cost-effective mode of transportation for the movement of small quantities of goods; (3) The cargo philosophy is designed to meet customer expectations by providing a convenient and personalised service that is focused on delivering goods directly to their door. This research employed theoretical methodologies to characterize the primary force exerted by vehicles in the transportation of bulk and liquid commodities (the relationship between centrifugal force and speed and the relationship between the center of gravity and speed). Furthermore, by using expert assessment, the significance indicators pertaining to the individual criteria impacting the transportation of bulk and liquid cargoes were ascertained, along with the identification of their interrelationships (comparison of the different forces in the transportation process of bulk and liquid cargoes, comparison of the criteria of centrifugal force in the transportation process of bulk and liquid cargoes, comparison of the dangerous factors in the transportation process of bulk and liquid cargoes, comparison of the critical level of tank filling in the transportation process of bulk and liquid cargoes, and comparison of the factors that can affect the dynamics of a vehicle in the transportation process of bulk and liquid cargoes).
Text Semantics-Driven Data Classification Storage Optimization
Authors: Yuan Zhu , Lv Xueqiang , Gong Yunchao , Liu Boshan , Yang Haixiang , You Xindong
Published: January 2024

Data classification storage has emerged as an effective strategy, harnessing the diverse performance attributes of storage devices to orchestrate a harmonious equilibrium between energy consumption, cost considerations, and user accessibility. The traditional strategy of solely relying on access frequency for data classification is no longer suitable for today’s complex storage environment. Diverging from conventional methods, we explore from the perspective of text semantics to address this issue and propose an effective data classification storage method using text semantic similarity to extract seasonal features. First, we adopt a dual-layer strategy based on semantic similarity to extract seasonal features. Second, we put forward a cost-effective data classification storage framework based on text seasonal features. We compare our work with the data classification approach AS-H, which runs at full high performance. In addition, we also compare it with K-ear, which adopts K-means as the classification algorithm. The experimental results show that compared with AS-H and K-ear, our method reduces energy consumption by 9.51–13.35% and operating costs by 13.20–22.17%.
Generating Stellar Spectra Using Neural Networks
Authors: Gebran Marwan
Published: January 2024

A new generative technique is presented in this paper that uses Deep Learning to reconstruct stellar spectra based on a set of stellar parameters. Two different Neural Networks were trained allowing the generation of new spectra. First, an autoencoder is trained on a set of BAFGK synthetic data calculated using ATLAS9 model atmospheres and SYNSPEC radiative transfer code. These spectra are calculated in the wavelength range of Gaia RVS between 8400 and 8800 Å. Second, we trained a Fully Dense Neural Network to relate the stellar parameters to the Latent Space of the autoencoder. Finally, we linked the Fully Dense Neural Network to the decoder part of the autoencoder and we built a model that uses as input any combination of Teff, logg, vesini, [M/H], and ξt and output a normalized spectrum. The generated spectra are shown to represent all the line profiles and flux values as the ones calculated using the classical radiative transfer code. The accuracy of our technique is tested using a stellar parameter determination procedure and the results show that the generated spectra have the same characteristics as the synthetic ones.
Detecting Relationship between the North–South Difference in Extreme Precipitation and Solar Cycle in China
Authors: Liu Jinjuan , Zhao Liang , Wang Jingsong , Xiao Ziniu
Published: January 2024

The sun plays a crucial role as the primary source of energy for the Earth’s climate system and the issue of the influence of solar activity on the climate has been actively discussed recently. However, the precise impact of solar activity on extreme precipitation on the decadal timescale remains insufficiently confirmed. In this study, we investigate the relationship between summer extreme precipitation events exceeding 20 mm (R20mm) in China and the 11-year sunspot number (SSN) cycle from 1951 to 2018. Results showed that the first mode of June–July R20mm, a “south-drought and north-flooding (SDNF)” distribution, exhibited a significant correlation with the SSN cycle (p = 0.02). The fundamental driver is likely the pronounced periodic response of stratospheric ozone to solar forcing. During summer of the high-solar-activity years (HSY), there is a notable increase in ozone concentration and high temperatures in the stratosphere, particularly in the Southern Hemisphere. This phenomenon leads to a layer of anomalous temperature inversion, suppressing convection at the subtropics. This induced downward anomalous airflow toward the north stimulates convective activity in the equatorial region and generates northward wave activities. These wave activities produce rising and sinking anomalies at different latitudes in the Northern Hemisphere troposphere, finally causing the “SDNF” pattern in China.
Overview of the Trajectory-Ensemble Potential Source Apportionment Web (TraPSA-Web) Toolkit for Atmospheric Pollutant Source Identification
Authors: Zhou Chuanlong , Zhou Hao , Hopke Philip K. , Holsen Thomas M.
Published: January 2024

Trajectory ensemble receptor models (TERMs) were widely used to determine the likely source locations and apportionment of air pollutants. This paper describes the development and applications of the Trajectory-ensemble Potential Source Apportionment Web application (TraPSA-Web), a comprehensive toolkit for likely atmospheric pollutant source location apportionments using TERMs and back trajectories generated with the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model. The TERMs integrated within the TraPSA-web include Concentration Field Analysis (CFA), Concentration Weighted Trajectory (CWT), single-site and multiple-site Potential Source Contribution Function (PSCF), and Simplified Quantitative Transport Bias Analysis (SQBA). TraPSA-Web is designed as a web application with a user-friendly modern graphical user interface (GUI), which largely enhances the accessibility to the users. TraPSA-Web will provide the air quality research community with a sophisticated toolkit for (1) easy management of the research project and datasets, (2) efficient automatization for HYSPLIT configurations, calculations, and result aggregations, (3) flexible configurations for the research scenarios and TERM parameters, and (4) interactive visualizations for the pollutant pattern analysis and TERM result mapping.
Real and Complex Potentials as Solutions to Planar Inverse Problem of Newtonian Dynamics
Authors: Kotoulas Thomas
Published: January 2024

We study the motion of a test particle in a conservative force field. In the framework of the 2D inverse problem of Newtonian dynamics, we find 2D potentials that produce a preassigned monoparametric family of regular orbits f(x,y)=c on the xy-plane (where c is the parameter of the family of orbits). This family of orbits can be represented by the “slope function” γ=fyfx uniquely. A new methodology is applied to the basic equation of the planar inverse problem in order to find potentials of a special form, i.e., V=F(x+y)+G(x−y), V=F(x+iy)+G(x−iy) and V=P(x)+Q(y), and polynomial ones. According to this methodology, we impose differential conditions on the family of orbits f(x,y) = c. If they are satisfied, such a potential exists and it is found analytically. For known families of curves, e.g., circles, parabolas, hyperbolas, etc., we find potentials that are compatible with them. We offer pertinent examples that cover all the cases. The case of families of straight lines is referred to.
On the Multi-Dimensional Sumudu-Generalized Laplace Decomposition Method and Generalized Pseudo-Parabolic Equations
Authors: Eltayeb Hassan
Published: January 2024

The essential goal of this work is to suggest applying the multi-dimensional Sumdu generalized Laplace transform decomposition for solving pseudo-parabolic equations. This method is a combination of the multi-dimensional Sumudu transform, the generalized Laplace transform, and the decomposition method. We provided some examples to show the effectiveness and the ability of this approach to solve linear and nonlinear problems. The results show that the proposed method is reliable and easy for obtaining approximate solutions of FPDEs and is more precise if we compare it with existing methods.
The Hallmarks of Cervical Cancer: Molecular Mechanisms Induced by Human Papillomavirus
Authors: Rosendo-Chalma Pedro , Antonio-Véjar Verónica , Ortiz Tejedor Jonnathan Gerardo , Ortiz Segarra Jose , Vega Crespo Bernardo , Bigoni-Ordóñez Gabriele Davide
Published: January 2024

Human papillomaviruses (HPVs) and, specifically, high-risk HPVs (HR-HPVs) are identified as necessary factors in the development of cancer of the lower genital tract, with CaCU standing out as the most prevalent tumor. This review summarizes ten mechanisms activated by HR-HPVs during cervical carcinogenesis, which are broadly associated with at least seven of the fourteen distinctive physiological capacities of cancer in the newly established model by Hanahan in 2022. These mechanisms involve infection by human papillomavirus, cellular tropism, genetic predisposition to uterine cervical cancer (CaCU), viral load, viral physical state, regulation of epigenetic mechanisms, loss of function of the E2 protein, deregulated expression of E6/E7 oncogenes, regulation of host cell protein function, and acquisition of the mesenchymal phenotype.
The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature
Authors: Munoz-Lopez Carlos , Wong Anne , Lewis Kieran , Bole Raevti , Vij Sarah C. , Lundy Scott D.
Published: January 2024

Male-factor infertility is implicated in over half of the millions of cases of infertility worldwide, and varicoceles are the most common correctable cause of male-factor infertility. The pathophysiologic mechanism for varicoceles is complex and next-generation technologies offer promising insights into the molecular underpinnings of this condition. In this narrative review, we highlight historical and contemporary paradigms associated with varicoceles, with an emphasis on the biological underpinnings of this disease. Specifically, we review the literature describing the underlying causes of varicoceles, discuss the molecular and cellular mechanisms causing pathological changes in some (but not all) men, and highlight key articles regarding the next-generation analyses (e.g., transcriptome, epigenome, proteome, and microbiome) being applied to better understand the condition and its treatment. These data demonstrate an ongoing evolution of the knowledge of varicoceles and the potential for improved personalized care in the future for men with this condition.
Role of Soil Microbiota Enzymes in Soil Health and Activity Changes Depending on Climate Change and the Type of Soil Ecosystem
Authors: Daunoras Jokūbas , Kačergius Audrius , Gudiukaitė Renata
Published: January 2024

The extracellular enzymes secreted by soil microorganisms play a pivotal role in the decomposition of organic matter and the global cycles of carbon (C), phosphorus (P), and nitrogen (N), also serving as indicators of soil health and fertility. Current research is extensively analyzing these microbial populations and enzyme activities in diverse soil ecosystems and climatic regions, such as forests, grasslands, tropics, arctic regions and deserts. Climate change, global warming, and intensive agriculture are altering soil enzyme activities. Yet, few reviews have thoroughly explored the key enzymes required for soil fertility and the effects of abiotic factors on their functionality. A comprehensive review is thus essential to better understand the role of soil microbial enzymes in C, P, and N cycles, and their response to climate changes, soil ecosystems, organic farming, and fertilization. Studies indicate that the soil temperature, moisture, water content, pH, substrate availability, and average annual temperature and precipitation significantly impact enzyme activities. Additionally, climate change has shown ambiguous effects on these activities, causing both reductions and enhancements in enzyme catalytic functions.
Review of Computational Fluid Dynamics Analysis in Biomimetic Applications for Underwater Vehicles
Authors: Zhang Zhijun , Wang Qigan , Zhang Shujun
Published: January 2024

Biomimetics, which draws inspiration from nature, has emerged as a key approach in the development of underwater vehicles. The integration of this approach with computational fluid dynamics (CFD) has further propelled research in this field. CFD, as an effective tool for dynamic analysis, contributes significantly to understanding and resolving complex fluid dynamic problems in underwater vehicles. Biomimetics seeks to harness innovative inspiration from the biological world. Through the imitation of the structure, behavior, and functions of organisms, biomimetics enables the creation of efficient and unique designs. These designs are aimed at enhancing the speed, reliability, and maneuverability of underwater vehicles, as well as reducing drag and noise. CFD technology, which is capable of precisely predicting and simulating fluid flow behaviors, plays a crucial role in optimizing the structural design of underwater vehicles, thereby significantly enhancing their hydrodynamic and kinematic performances. Combining biomimetics and CFD technology introduces a novel approach to underwater vehicle design and unveils broad prospects for research in natural science and engineering applications. Consequently, this paper aims to review the application of CFD technology in the biomimicry of underwater vehicles, with a primary focus on biomimetic propulsion, biomimetic drag reduction, and biomimetic noise reduction. Additionally, it explores the challenges faced in this field and anticipates future advancements.
Hybrid Nanomaterials: A Brief Overview of Versatile Solutions for Sensor Technology in Healthcare and Environmental Applications
Authors: Godja Norica-Carmen , Munteanu Florentina-Daniela
Published: January 2024

The integration of nanomaterials into sensor technologies not only poses challenges but also opens up promising prospects for future research. These challenges include assessing the toxicity of nanomaterials, scalability issues, and the seamless integration of these materials into existing infrastructures. Future development opportunities lie in creating multifunctional nanocomposites and environmentally friendly nanomaterials. Crucial to this process is collaboration between universities, industry, and regulatory authorities to establish standardization in this evolving field. Our perspective favours using screen-printed sensors that employ nanocomposites with high electrochemical conductivity. This approach not only offers cost-effective production methods but also allows for customizable designs. Furthermore, incorporating hybrids based on carbon-based nanomaterials and functionalized Mxene significantly enhances sensor performance. These high electrochemical conductivity sensors are portable, rapid, and well-suited for on-site environmental monitoring, seamlessly aligning with Internet of Things (IoT) platforms for developing intelligent systems. Simultaneously, advances in electrochemical sensor technology are actively working to elevate sensitivity through integrating nanotechnology, miniaturization, and innovative electrode designs. This comprehensive approach aims to unlock the full potential of sensor technologies, catering to diverse applications ranging from healthcare to environmental monitoring. This review aims to summarise the latest trends in using hybrid nanomaterial-based sensors, explicitly focusing on their application in detecting environmental contaminants.
Coexisting Biopsy-Diagnosed Dementia and Glioblastoma
Authors: Fetcko-Fayad Kaleigh , Batich Kristen , Reitman Zachary J. , Walsh Kyle M. , Chamberlin Gregory , Smith Vanessa , Jones Karra , Cummings Thomas , Peters Katherine B.
Published: January 2024

Both glioblastoma (GBM) and dementia are devastating diseases with limited treatments that are usually not curative. Having clinically diagnosed dementia with an associated biopsy-proven etiology and a coexisting GBM diagnosis is a rare occurrence. The relationship between the development of neurodegenerative dementia and GBM is unclear, as there are conflicting reports in the literature. We present two cases of simultaneous biopsy-proven dementia, one with Alzheimer’s disease (AD) and GBM, and one with cerebral amyloid angiopathy (CAA) and GBM. We discuss how these diseases may be associated. Whether one pathologic process begins first or develops concurrently is unknown, but certain molecular pathways of dementia and GBM appear directly related while others inversely related. Further investigations of these close molecular relationships between dementia and GBM could lead to development of improved diagnostic tools and therapeutic interventions for both diseases.
Mental Health Disparities among Pre-Clinical Medical Students at Saint Louis University during the COVID-19 Pandemic
Authors: Chwa Won Jong , Chong Albert C. , Lin Sheryl , Su Erin H. , Sheridan Chantal , Schreiber Jacob , Zia Stephanie K. , Thompson Keniesha
Published: January 2024

The COVID-19 pandemic disproportionately affected racial and ethnic minorities. Medical students were also particularly impacted as they coped with increased stressors due to delayed medical training and a high prevalence of mental health conditions. This study investigates mental health disparities of underrepresented in medicine (URM) students at the Saint Louis University School of Medicine (SLUSOM). An anonymous online survey was distributed to first- and second-year medical students at SLUSOM in February 2021. The survey queried demographic information, lifestyle factors, and pandemic-related and institutional concerns. Mental health was assessed via the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9). Statistical tests were run with SPSS, version 27. A convenience sample of 87 students responded to the survey. Students who were categorized as URM were significantly more likely to be at risk of major depressive disorder during the pandemic. Concern about a lack of financial support was significantly greater among students categorized as URM. Concerns regarding a lack of financial support, mental health support, and decreased quality of medical training significantly predicted PHQ-9 scores. Our findings revealed several key factors that may exacerbate mental health disparities among URM students during the pandemic. Providing adequate financial and academic resources for URMs may improve mental health outcomes for similar adverse events in the future.
Seismic Performance of Reinforced Concrete Frames with Added Floors: Emphasizing the Influence of Structural Joints in the Context of Sustainable Vertical Extensions
Authors: Shala Alush , Bleiziffer Jelena
Published: January 2024

The size of the population and the need for residential spaces are increasing. One possible solution is to add new floors to existing buildings. This research examines the seismic behavior of reinforced concrete frame structures that have undergone vertical extensions by adding extra floors. The primary focus is on the joints that connect these extensions to the existing structure and the appropriate modeling of these joints. However, adding floors to existing structures might be structurally challenging, especially in terms of the behavior under seismic actions. This paper presents a numerical study of a reinforced concrete frame in an old building to which new floors are subsequently added. The analysis shows that the frame does not behave as a whole with the old part of the structure, nor does it behave the same as if it were made with rigid joints compared to additional ones connected using hinge joints. It is noted that in structural analyses, the connection between an existing structure and a vertical extension is often considered rigid, yet in practice, these joints may behave differently. The change from the corner (knee) joint to the external joint has its own effect on the distribution of internal forces in the structure as a whole and in the joint in particular. Compared to demolishing and rebuilding, vertical extension is considered environmentally friendly, reducing the financial costs, environmental pollution, and waste generation.
HER2-Low Expression in Male Breast Cancer: Results from a Multicenter Series in Italy
Authors: Silvestri Valentina , Valentini Virginia , Bucalo Agostino , Conti Giulia , Manzella Livia , Turchetti Daniela , Russo Antonio , Capalbo Carlo , Ottini Laura
Published: January 2024

In the field of breast cancer care, a significant breakthrough has occurred with the recognition of HER2-low expression as a target for novel anti-HER2 antibody–drug conjugates (ADC). This discovery is reshaping the treatment landscape, challenging previous perceptions that considered HER2-low as clinically insignificant. The ability to target HER2-low expression is expected to have substantial clinical implications, irrespective of gender, including in cases of male breast cancer (MBC). However, an estimate of the prevalence of the HER2-low subtype in MBC is missing. This retrospective, observational, multicenter study was aimed at characterizing the HER2-low subtype in MBC. For the purpose of this study, the three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) was used to reclassify the HER2-negative group into HER-0 or HER2-low subtypes. In the whole series of 144 invasive MBCs, 79 (54.9%) were HER2-0 (IHC scores of 0), 39 (27.1%) HER2-low (IHC scores of 1+/2+ with negative ISH), and 26 (18.0%) HER2-positive (IHC scores of 3+/2+ with positive ISH). Specifically, among hormone receptor-positive (HR+) HER2-negative invasive MBCs, 34.8% were HER2-low and 65.2% HER2-0. Compared with HER2-0, HER2-low subtype was associated with a positive lymph node involvement (p = 0.01). Other pathologic characteristics including histology, staging, and grading did not show notable variations between the two subtypes. The presence of germline BRCA1/2 pathogenic variants (PVs) did not significantly differ between HER2-0 and HER2-low MBCs. However, about 13% of HER2-low MBCs had germline PVs in BRCA1/2 genes, mainly BRCA2, a clinically relevant observation in the context of combined target therapy. Overall, our data, which focused on the largest gender-specific breast cancer series, to our knowledge, confirm that the emerging three-tiered categorization of HER2 (HER2-0, HER2-low, and HER2-positive) can also be considered in MBC, to mitigate both the gender gap and the underrepresentation of males in clinical trials.
Sensitive and Specific Analyses of Colorectal Cancer Recurrence through Multiplex superRCA Mutation Detection in Blood Plasma
Authors: Sandberg Emma , Nunes Luís , Edqvist Per-Henrik , Mathot Lucy , Chen Lei , Edgren Tomas , Al Nassralla Shahed , Glimelius Bengt , Landegren Ulf , Sjöblom Tobias
Published: January 2024

Mutation analysis of circulating tumor DNA (ctDNA) has applications in monitoring of colorectal cancer (CRC) patients for recurrence. Considering the low tumor fraction of ctDNA in cell-free DNA (cfDNA) isolated from blood plasma, the sensitivity of the detection method is important. Here, plasma DNA collected at diagnosis and follow-up from 25 CRC patients was analyzed using a multiplex superRCA mutation detection assay. The assay was also performed on genomic DNA (gDNA) from tumor and normal tissue from 20 of these patients. The lower limit of detection for most sequence variants was in the range of 10−5, while when analyzing cfDNA from plasma with a typical input of 33 ng, the practical detection limit was ~10−4 or 0.01% mutant allele frequency (MAF). In 17 of 19 patients with identified hotspot mutations in tumor gDNA, at least one hotspot mutation could be detected in plasma DNA at the time of diagnosis. The MAF increased at subsequent time points in four of the patients who experienced a clinical relapse. Multiplex superRCA analysis of the remaining six patients did not reveal any hotspot mutations. In conclusion, multiplex superRCA assays proved suitable for monitoring CRC patients by analyzing hotspot mutations in cfDNA, and dynamic changes in MAF were observed in patients with clinical relapse.
Efficacy of Immune Checkpoint Inhibitors vs. Tyrosine Kinase Inhibitors/Everolimus in Adjuvant Renal Cell Carcinoma: Indirect Comparison of Disease-Free Survival
Authors: Ossato Andrea , Gasperoni Lorenzo , Del Bono Luna , Messori Andrea , Damuzzo Vera
Published: January 2024

Background: The proven efficacy of mTOR inhibitors (mTORIs), tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in metastatic renal cell carcinoma (RCC) suggests that these agents should be investigated as adjuvant therapy with the aim of eliminating undetectable microscopic residual disease after curative resection. The aim of our study was to compare the efficacy of these treatments using an innovative method of reconstructing individual patient data. Methods: Nine phase III trials describing adjuvant RCC treatments were selected. The IPDfromKM method was used to reconstruct individual patient data from Kaplan–Meier (KM) curves. The combination treatments were compared with the control arm (placebo) for disease-free survival (DFS). Multi-treatment KM curves were used to summarize the results. Standard statistical tests were performed. These included hazard ratio and likelihood ratio tests for heterogeneity. Results: In the overall population, the study showed that two ICIs (nivolumab plus ipilimumab and pembrolizumab) and one TKI (sunitinib) were superior to the placebo, whereas both TKIs and mTORIs were inferior. As we assessed DFS as the primary endpoint for the adjuvant comparison, the overall survival benefit remains unknown. Conclusions: This novel approach to investigating survival has allowed us to conduct all indirect head-to-head comparisons between these agents in a context where no “real” comparative trials have been conducted.
Geriatric Assessment of Older Patients Receiving Trabectedin in First-Line Treatment for Advanced Soft Tissue Sarcomas: The E-TRAB Study from The German Interdisciplinary Sarcoma Group (GISG-13)
Authors: Kasper Bernd , Pink Daniel , Rothermundt Christian , Richter Stephan , Augustin Marinela , Kollar Attila , Kunitz Annegret , Eisterer Wolfgang , Gaidzik Verena , Brodowicz Thomas , Egerer Gerlinde , Reichardt Peter , Hohenberger Peter , Schuler Markus K.
Published: January 2024

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.
CT Images in Follicular Lymphoma: Changes after Treatment Are Predictive of Cardiac Toxicity in Patients Treated with Anthracycline-Based or R-B Regimens
Authors: Esposito Fabiana , Mezzanotte Valeria , Tesei Cristiano , Luciano Alessandra , Gigliotti Paola Elda , Nunzi Andrea , Secchi Roberto , Angeloni Cecilia , Pitaro Maria , Meconi Federico , Cerocchi Martina , Garaci Francesco , Venditti Adriano , Postorino Massimiliano , Chiocchi Marcello
Published: January 2024

The aim of this study is to evaluate changes in epicardial adipose tissue (EAT) and cardiac extracellular volume (ECV) in patients with follicular lymphoma (FL) treated with R-CHOP-like regimens or R-bendamustine. We included 80 patients with FL between the ages of 60 and 80 and, using computed tomography (CT) performed at onset and at the end of treatment, we assessed changes in EAT by measuring tissue density at the level of the cardiac apex, anterior interventricular sulcus and posterior interventricular sulcus of the heart. EAT is known to be associated with metabolic syndrome, increased calcium in the coronary arteries and therefore increased risk of coronary artery disease. We also evaluated changes in ECV, which can be used as an early imaging marker of cardiac fibrosis and thus myocardial damage. The R-CHOP-like regimen was associated with lower EAT values (p < 0.001), indicative of a less active metabolism and more adipose tissue, and an increase in ECV (p < 0.001). Furthermore, in patients treated with anthracyclines and steroids (R-CHOP-like) there is a greater decrease in ejection fraction (EF p < 0.001) than in the R-B group. EAT and ECV may represent early biomarkers of cardiological damage, and this may be considered, to our knowledge, the first study investigating radiological and cardiological parameters in patients with FL.
G Protein-Coupled Receptors and Ion Channels Involvement in Cisplatin-Induced Peripheral Neuropathy: A Review of Preclinical Studies
Authors: Becker Gabriela , Atuati Samuel Felipe , Oliveira Sara Marchesan
Published: January 2024

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.
Multiparametric Radiogenomic Model to Predict Survival in Patients with Glioblastoma
Authors: Mahmoudi Keon , Kim Daniel H. , Tavakkol Elham , Kihira Shingo , Bauer Adam , Tsankova Nadejda , Khan Fahad , Hormigo Adilia , Yedavalli Vivek , Nael Kambiz
Published: January 2024

Background: Clinical, histopathological, and imaging variables have been associated with prognosis in patients with glioblastoma (GBM). We aimed to develop a multiparametric radiogenomic model incorporating MRI texture features, demographic data, and histopathological tumor biomarkers to predict prognosis in patients with GBM. Methods: In this retrospective study, patients were included if they had confirmed diagnosis of GBM with histopathological biomarkers and pre-operative MRI. Tumor segmentation was performed, and texture features were extracted to develop a predictive radiomic model of survival (<18 months vs. ≥18 months) using multivariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regularization to reduce the risk of overfitting. This radiomic model in combination with clinical and histopathological data was inserted into a backward stepwise logistic regression model to assess survival. The diagnostic performance of this model was reported for the training and external validation sets. Results: A total of 116 patients were included for model development and 40 patients for external testing validation. The diagnostic performance (AUC/sensitivity/specificity) of the radiomic model generated from seven texture features in determination of ≥18 months survival was 0.71/69.0/70.3. Three variables remained as independent predictors of survival, including radiomics (p = 0.004), age (p = 0.039), and MGMT status (p = 0.025). This model yielded diagnostic performance (AUC/sensitivity/specificity) of 0.77/81.0/66.0 (training) and 0.89/100/78.6 (testing) in determination of survival ≥ 18 months. Conclusions: Results show that our radiogenomic model generated from radiomic features at baseline MRI, age, and MGMT status can predict survival ≥ 18 months in patients with GBM.
Corrosion at the Steel–Medium Interface
Authors: Melchers Robert E.
Published: January 2024

Corrosion on the interface between a metal alloy, such as steel, and a wet, permeable non-metallic medium is of considerable practical interest. Examples include the interface between steel and water, the atmosphere or concrete, as for steel reinforcement bars; between metal and soil, as for buried cast iron or steel pipes; deposits of some type, as in under-deposit corrosion; and the interface with insulation, protective coatings, or macro- or micro-biological agents. In all cases, corrosion initiation depends on the characteristics of the interfacial zone, both of the metal and the medium, and the spatial variability. For (near-)homogeneous semi-infinite media with good interfacial contact, the pitting, crevices and general corrosion of the metal will be largely controlled by the metal (micro-)characteristics, including its inclusions, imperfections and surface roughness. In other cases, these may be overshadowed by the macro-characteristics of the medium and the degree of interfacial contact, possibly with severe resulting corrosion. Where the build-up of corrosion products can occur at the interface, they will dominate longer-term corrosion and govern the long-term corrosion rate. For media of finite thickness, diffusion issues and material deterioration may also be involved. The practical implications are outlined. It is argued that with the presence of a suitable medium, it is possible to achieve negligible long-term corrosion but only if certain practical actions are taken.
The Early Performance Development of Hot In-Place Recycled Asphalt Mixture
Authors: Shi Qijia , Liu Chaochao , Xue Yanhua , Xue Yiyang , Zhang Chen , Lu Wenlong , Wen Yiyi , Lv Songtao
Published: January 2024

With increasing societal attention being directed to resource and environment problems, the research focus on high reclaimed asphalt content mixtures has become pertinent. The degree of asphalt fusion in the thermal regeneration process of a high RAP content reclaimed asphalt mixture has a great influence on its performance. In order to explore the development process of hot in-place recycling mixture performance along with internal asphalt fusion, this study conducted research on a geothermal regeneration mixture with 80% RAP content. Dynamic shear rheology (DSR), infrared spectroscopy, and scanning electron microscopy were used to investigate the fusion of recycled mixture under different placement times (1 day, 4 days, and 7 days), and the road performance and fatigue life of the recycled mixture under different placement times were then studied. The results showed that the fusion degree of old asphalt and new asphalt in a recycled asphalt mixture reached 100%, and gradually increased with the extension of placement time. With the increase in placement time, the high temperature performance of the regenerated mixture gradually decreased, the water stability gradually increased, and the low-temperature performance and fatigue life significantly increased from 1 day to 7 days, by 19% and 32%, respectively.
Effects of Bias Voltages on the Tribological Behaviors of DLC Coatings
Authors: Zhang Shuling , Huang Tenglong , Sun Shengdi , Wu Shuaizheng , Yang Xiangdong , Guo Feng , Zhang Bo , Dai Longjie
Published: January 2024

Ti/TiN/(Ti,N)-DLC/Ti-DLC/DLC coatings were deposited on 431 stainless steel using direct current magnetron sputtering technology under different bias voltages(0 V, −100 V, −200 V and −300 V). The microstructure and tribocorrosion performance of these DLC coatings in seawater was investigated. The results indicated that under the bias voltages, a denser and smoother surface of DLC coatings with a higher bonding strength between coatings and substrates was observed related to the increased incident kinetic energy of deposited ionized atoms. When the bias voltage was −200 V, the surface roughness reduced from 9.81 nm to 7.03 nm, and the bonding strength enhanced from 8.23 N to 8.86 N. What is more, the sp3 bond proportion and the disorder degree in DLC coatings both increased, which resulted in improved hardness and deformation resistance. However, when the bias voltage was −300 V, the increase of the amorphization was associated with a simultaneous rise in internal stress, which reduced the hardness and bond strength a little (8.72 N). DLC coatings can effectively improve the tribocorrosion properties of 431 stainless steel in seawater. When the voltage was −200 V, the average friction coefficient decreased from 0.35 to 0.07, with shallower wear traces and the wear loss of the DLC coating also being the smallest. The abrasive wear caused by metal oxides falling off the grinding ball, and the plastic deformation of the DLC coatings are the main wear forms. The high-density structure of DLC coatings under bias voltages can not only prevent the rapid expansion of cracks during deformation, but also provides a physical barrier to the erosion, which improves the corrosion and friction resistance in seawater. The optimization of bias voltage can improve the tribological performance of DLC coatings by regulating the carbon chain bond and microstructure. These results provide reference for DLC preparation and their potential engineering applications in stainless steel.