bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Microbial Additive Supplementation on Growth Performance, Blood Metabolites, Fecal Microflora, and Carcass Characteristics of Growing–Finishing Pigs
Authors: Lee Hyuk-Jun , Choi Bu-Gil , Joo Young-Ho , Baeg Chang-Hyun , Kim Ji-Yoon , Kim Dong-Hyeon , Lee Seong-Shin , Kim Sam-Churl
Published: April 2024

This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing–finishing pigs. A total of 180 growing–finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing–finishing pigs.
Research of Park and Ride Parking Spaces Tiered Pricing Methodology Based on Subway Ride Distance
Authors: Miao Hao , Guan Hongzhi , Han Yan , Wang Hongfei
Published: April 2024

Park and Ride (P&R) as a demand management tool has the effect of reducing traffic congestion in urban centers, saving energy and reducing pollutant emissions. Since 2000, many cities in China have been constructing P&R facilities, which have partially alleviated urban traffic congestion and provided a time-reliable mode of travel for commuters heading to urban centers. However, in recent years, due to the pricing policy of the P&R facility, there has been an insufficient supply of P&R facilities in many places. In fact, the P&R system prefers to welcome travelers who make long-distance subway rides and does not want those who make short-distance subway rides to occupy more parking spaces. To address this, this paper proposes a tiered pricing strategy that considers charging parking fees based on the distance traveled by commuters after switching to public transportation, to improve the utilization of P&R. That is, charge less for parking for long-distance subway riders and more for short-distance subway riders. Firstly, based on questionnaire data from SP surveys, a fixed pricing mixed logit model (FP model) and a tiered pricing mixed logit model (TP model) for P&R facilities are constructed. Utilizing two models, we explored the mechanisms underpinning traveler’s mode choice influenced by daily habits and travel considerations through the comparison of the two models to validate the effectiveness of the tiered pricing for P&R facilities. The study found that the implementation of a tiered pricing method for P&R facilities increases its attractiveness to long-distance subway ride travelers, resulting in a higher proportion of long-distance subway riders among P&R commuters. In the study’s last section, a marginal effect analysis was conducted on the per-kilometer cost (Pkm) within the P&R model. This analysis determined the optimal Pkm for three subway travel distances within the P&R model. Consequently, it calculated the corresponding P&R parking fees for these three subway travel distances. Additionally, we have predicted the implementation effects of the tiered pricing scheme.
Decentralized Identity Authentication Mechanism: Integrating FIDO and Blockchain for Enhanced Security
Authors: Ou Hsia-Hung , Pan Chien-Hsiu , Tseng Yang-Ming , Lin Iuon-Chang
Published: April 2024

FIDO (Fast Identity Online) is a set of network identity standards established by the FIDO Alliance. It employs a framework based on public key cryptography to facilitate multi-factor authentication (MFA) and biometric login, ensuring the robust protection of personal data associated with cloud accounts and ensuring the security of server-to-terminal device protocols during the login process. The FIDO Alliance has established three standards: FIDO Universal Second Factor (FIDO U2F), FIDO Universal Authentication Framework (FIDO UAF), and the Client to Authenticator Protocols (CTAP). The newer CTAP, also known as FIDO2, integrates passwordless login and two-factor authentication. Importantly, FIDO2’s support for major browsers enables users to authenticate their identities via FIDO2 across a broader range of platforms and devices, ushering in the era of passwordless authentication. In the FIDO2 framework, if a user’s device is stolen or compromised, then the private key may be compromised, and the public key stored on the FIDO2 server may be tampered with by attackers attempting to impersonate the user for identity authentication, posing a high risk to information security. Recognizing this, this study aims to propose a solution based on the FIDO2 framework, combined with blockchain technology and access control, called the FIDO2 blockchain architecture, to address existing security vulnerabilities in FIDO2. By leveraging the decentralized nature of the blockchain, the study addresses potential single points of failure in FIDO2 server centralized identity management systems, thereby enhancing system security and availability. Furthermore, the immutability of the blockchain ensures the integrity of public keys once securely stored on the chain, effectively reducing the risk of attackers impersonating user identities. Additionally, the study implements an access control mechanism to manage user permissions effectively, ensuring that only authorized users can access corresponding permissions and preventing unauthorized modifications and abuse. In addition to proposing practical solutions and steps, the study explains and addresses security concerns and conducts performance evaluations. Overall, this study brings higher levels of security and trustworthiness to FIDO2, providing a robust identity authentication solution.
New Fat Bases in Model Emulsion Systems in Physicochemical and Consumer Evaluation
Authors: Kowalska Małgorzata , Woźniak Magdalena , Turek Paweł , Żbikowska Anna
Published: April 2024

The purpose of this study was to indicate the validity of using enzymatically interesterified fats as a fat emulsion base. A study was conducted to determine the stability of emulsion systems based on enzymatically interesterified fats and fats containing mixed fats. The fats used in the modifications were mutton tallow and hemp oil. It was found that emulsions based on esterified fats, regardless of the type of modified fat, showed a higher shelf life and had high homogeneity. On the other hand, emulsions based on mixed fats already showed destabilization characteristics in the first days. Their structure was heterogeneous. Microscopic evaluation clearly showed large droplets of the dispersed phase, indicating a tendency to delaminate. Consumer evaluation showed that the sensory quality of the presented emulsion systems based on enzymatically interesterified fats was fully accepted by the participating consumers. Based on the results of the study, it was concluded that all of the consumer-evaluated emulsions received good or very good acceptance in terms of the sensory characteristics evaluated.
A Method for Identifying the Wear State of Grinding Wheels Based on VMD Denoising and AO-CNN-LSTM
Authors: Xu Kai , Feng Dinglu
Published: April 2024

Monitoring the condition of the grinding wheel in real-time during the grinding process is crucial as it directly impacts the precision and quality of the workpiece. Deep learning technology plays a vital role in analyzing the changes in sensor signals and identifying grinding wheel wear during the grinding process. Therefore, this paper innovatively proposes a grinding wheel wear recognition method based on Variational Mode Decomposition (VMD) denoising and Aquila Optimizer—Convolutional Neural Network—Long Short-Term Memory (AO-CNN-LSTM). The paper utilizes Acoustic Emission (AE) signals generated during grinding to identify the condition of the grinding wheel. To address noise interference, the study introduces the VMD algorithm for denoising the sample dataset, enhancing the effectiveness of neural network training. Subsequently, the dataset is fed into the designed Convolutional Neural Network—Long Short-Term Memory (CNN-LSTM) structure with AO-optimized parameters. Experimental results demonstrate that this method achieves high accuracy and performance.
Barley Malt as a Binder for Moulding Sands—Gas Evolution and Surface Quality of Iron Castings
Authors: Nowak Daniel , Bobrowski Artur , Samociuk Bartłomiej , Żymankowska-Kumon Sylwia , Medyński Daniel
Published: April 2024

The requirements placed on the foundry industry are mainly related to the need to maintain an appropriate quality–price ratio of the product and to maintain an appropriate production regime that takes into account modern legal solutions related to environmental protection. This work is part of the trend of searching for new or previously unused materials from renewable sources in moulding sand technology. This article concerns the possibility of using barley malt in moulding material technology as a binding material. The presented work contains the results of research on the release of gases during casting, where high temperatures cause the decomposition of chemical substances. The tests confirmed that moulding sands with barley malt as a binder do not cause excessive emissions of harmful gaseous products when pouring moulds with liquid casting alloy. The volume of gases formed was smaller than that of commonly used moulding sands with other binders. The total volume of gases produced and the kinetics of their release indicate that casting in this type of moulding sand did not cause any technological inconvenience or casting defects of gaseous origin. This was confirmed by research involving obtaining iron castings in industrial conditions using barley malt as a binder in moulding sand technology, which were then subjected to visual assessment and roughness analysis.
A Generative Deep Learning Approach for Improving the Mechanical Performance of Structural Components
Authors: Yüksel Nurullah , Börklü Hüseyin Rıza
Published: April 2024

This study aimed to improve the mechanical properties of 3D concept designs by combining the design capability of a generative adversarial network with finite element analysis. This approach offers an innovative perspective on the conditioning of generative models while improving design properties and automation. A new design and evaluation framework has been developed for GAN models to generate 3D models with improved mechanical properties. The framework is an iterative process that includes dataset generation, GAN training, and finite element analysis. A “joint” component used in the aerospace industry is considered to demonstrate the proposed method’s effectiveness. Over six iterations, an increase of 20% is recorded in the average safety factor of the designs, and the variety of designs produced is narrowed in the desired direction. These findings suggest that the direct generation of structural components with generative models can expand the potential of deep learning in engineering design. Another innovative aspect of this study is that it provides a new option for the conditioning of data-dependent generative design models.
Impacts of Climate Change on Runoff in the Heihe River Basin, China
Authors: Liu Qin , Cheng Peng , Lyu Meixia , Yan Xinyang , Xiao Qingping , Li Xiaoqin , Wang Lei , Bao Lili
Published: April 2024

Located in the central part of the arid regions of Northwest China, the Heihe River Basin (HRB) plays an important role in wind prevention, sand fixation, and soil and water conservation as the second largest inland river basin. In the context of the warming and wetting climate observed in Northwest China, the situation of the ecological environment in the HRB is of significant concern. Using the data from meteorological observation stations, grid fusion and hydrological monitoring, this study analyzes the multi-scale climate changes in the HRB and their impacts on runoff. In addition, predictive models for runoff in the upper and middle reaches were developed using machine learning methods. The results indicate that the climate in the HRB has experienced an overall warming and wetting trend over the past 60 years. At the same time, there are clear regional variabilities in the climate changes. Precipitation shows decreasing trends in the northwestern part of the HRB, while it shows increases at rates higher than the regional average in the southeastern part. Moreover, the temperature increases are generally smaller in the upper reaches than those in the middle and lower reaches. Over the past 60 years, there has been a remarkable increase in runoff at the Yingluo Gorge (YL) hydrological station, which exhibits a distinct “single-peak” pattern in the variation of monthly runoff. The annual runoff volume at the YL (ZY) hydrological station is significantly correlated with the precipitation in the upper (middle) reaches, indicating the precipitation is the primary influencing factor determining the annual runoff. Temperature has a significant impact only on the runoff in the upper reaches, while its impact is not significant in the middle reaches. The models trained by the support vector machines and random forest models perform best in predicting the annual runoff and monthly runoff, respectively. This study can provide a scientific basis for environmental protection and sustainable development in the HRB.
Optic Nerve Head Pulsatile Displacement in Open-Angle Glaucoma after Intraocular Pressure Reduction Measured by Optical Coherence Tomography: A Pilot Study
Authors: Masís Solano Marissé , Richer Emmanuelle , Costantino Santiago , Lesk Mark R.
Published: April 2024

This study investigated the effect of intraocular pressure (IOP) reduction on pulsatile displacement within the optic nerve head (ONH) in primary open-angle glaucoma (POAG) patients with and without axial myopia. Forty-one POAG patients (19 without myopia, 9 with axial myopia and 13 glaucoma with no intervention) participated. Swept-source optical coherence tomography (OCT) videos of the ONH were obtained before and after IOP-lowering treatment (medical or surgical) achieving a minimum IOP drop of 3 mmHg. A demons registration-based algorithm measured local pulsatile displacement maps within the ONH. Results demonstrated a significant 14% decrease in pulsatile tissue displacement in the non-myopic glaucoma cohort after intervention (p = 0.03). However, glaucoma patients with axial myopia exhibited no statistically significant change. There were no significant changes in the pulsatile ONH deformation in the control group. These findings suggest a potential link between IOP reduction and reduced pulsatile displacement within the ONH in POAG patients without myopia, offering new insights into the disease’s pathophysiology and warranting further investigation into underlying mechanisms and clinical implications.
Muscle Transcriptome Analysis of Mink at Different Growth Stages Using RNA-Seq
Authors: Rong Min , Xing Xiumei , Zhang Ranran
Published: April 2024

Mink is a kind of small and precious fur animal resource. In this study, we employed transcriptomics technology to analyze the gene expression profile of mink pectoral muscle tissue, thereby elucidating the regulatory mechanisms underlying mink growth and development. Consequently, a total of 25,954 gene expression profiles were acquired throughout the growth and development stages of mink at 45, 90, and 120 days. Among these profiles, 2607 genes exhibited significant differential expression (|log2(fold change)| ≥ 2 and p_adj < 0.05). GO and KEGG enrichment analyses revealed that the differentially expressed genes were primarily associated with the mitotic cell cycle process, response to growth factors, muscle organ development, and insulin resistance. Furthermore, GSEA enrichment analysis demonstrated a significant enrichment of differentially expressed genes in the p53 signaling pathway at 45 days of age. Subsequent analysis revealed that genes associated with embryonic development (e.g., PEG10, IGF2, NRK), cell cycle regulation (e.g., CDK6, CDC6, CDC27, CCNA2), and the FGF family (e.g., FGF2, FGF6, FGFR2) were all found to be upregulated at 45 days of age in mink, which suggested a potential role for these genes in governing early growth and developmental processes. Conversely, genes associated with skeletal muscle development (PRVA, TNNI1, TNNI2, MYL3, MUSTN1), a negative regulator of the cell cycle gene (CDKN2C), and IGFBP6 were found to be up-regulated at 90 days of age, suggesting their potential involvement in the rapid growth of mink. In summary, our experimental data provide robust support for elucidating the regulatory mechanisms underlying the growth and development of mink.
Knockdown H19 Accelerated iPSCs Reprogramming through Epigenetic Modifications and Mesenchymal-to-Epithelial Transition
Authors: Sun Ruizhen , Zhang Ximei , Gong Tiantian , Zhang Yue , Wang Qi , He Chenyao , Ju Jielan , Jin Chunmiao , Ding Wenxin , Gao Jingnan , Shen Jingling , Li Qiuming , Shan Zhiyan
Published: April 2024

H19 is an essential imprinted gene that is expressed to govern normal embryonic development. During reprogramming, the parental pronuclei have asymmetric reprogramming capacities and the critical reprogramming factors predominantly reside in the male pronucleus. After inhibiting the expression of H19 and Gtl2, androgenetic haploid ESCs (AG-haESCs) can efficiently and stably support the generation of healthy SC pups at a rate of ~20%, and double-knockout parthenogenetic haESCs can also produce efficiently. Induced pluripotent stem (iPS) cell reprogramming is thought to have a characteristic epigenetic pattern that is the reverse of its developmental potential; however, it is unclear how H19 participates in iPS cell reprogramming. Here, we showed that the expression of H19 was transiently increased during iPSC reprogramming. H19 knockdown resulted in greater reprogramming efficiency. The genes associated with pluripotency showed enhanced expression during the early reprogramming process, and the Oct4 promoter was demethylated by bisulfite genomic sequencing analysis. Moreover, expression analysis revealed that the mesenchymal master regulators associated with epithelial-to-mesenchymal transition (EMT) were downregulated during reprogramming in H19 knockdown. These findings provide functional insight into the role of H19 as a barrier to the early reprogramming process.
Effect of SGLT2-Inhibitors on Polygraphic Parameters in Elderly Patients Affected by Heart Failure, Type 2 Diabetes Mellitus, and Sleep Apnea
Authors: Armentaro Giuseppe , Pelaia Corrado , Condoleo Valentino , Severini Giandomenico , Crudo Giulia , De Marco Mario , Pastura Carlo Alberto , Tallarico Valeria , Pezzella Rita , Aiello Domenico , Miceli Sofia , Maio Raffaele , Savarese Gianluigi , Rosano Giuseppe M. C. , Sciacqua Angela
Published: April 2024

Obstructive sleep apneas (OSAs) and central sleep apneas (CSAs) are the most common comorbidities in Heart Failure (HF) that are strongly associated with all-cause mortality. Several therapeutic approaches have been used to treat CSA and OSA, but none have been shown to significantly improve HF prognosis. Our study evaluated the effects of a 3-months treatment with sodium-glucose cotransporter type 2 inhibitor (SGLT2i) on polygraphic parameters in patients with sleep apnea (SA) and HF, across the spectrum of ejection fraction, not treated with continuous positive air pressure (CPAP). A group of 514 consecutive elderly outpatients with HF, type 2 diabetes mellitus (T2DM) and SA, eligible for treatment with SGLT2i, were included in the investigation before starting any CPAP therapy. The two groups were compared with the t-test and Mann–Whitney test for unpaired data when appropriate. Then, a simple logistic regression model was built using 50% reduction in AHI as the dependent variable and other variables as covariates. A multivariate stepwise logistic regression model was constructed using the variables that linked with the dependent variable to calculate the odds ratio (OR) for the independent predictors associated with the reduction of 50% in AHI. The treated group experienced significant improvements in polygraphic parameters between baseline values and follow-up with reduction in AHI (28.4 ± 12.9 e/h vs. 15.2 ± 6.5 e/h; p < 0.0001), ODI (15.4 ± 3.3 e/h vs. 11.1 ± 2.6 e/h; p < 0.0001), and TC90 (14.1 ± 4.2% vs. 8.2 ± 2.0%; p < 0.0001), while mean SpO2 improved (91. 3 ± 2.3 vs. 93.8 ± 2.5); p < 0.0001. These benefits were not seen in the untreated population. The use of SGLT2i in patients suffering from HF and mixed-type SA not on CPAP therapy significantly contributes to improving polygraphic parameters.
Understanding and Perception of Automated Text Generation among the Public: Two Surveys with Representative Samples in Germany
Authors: Lermann Henestrosa Angelica , Kimmerle Joachim
Published: April 2024

Automated text generation (ATG) technology has evolved rapidly in the last several years, enabling the spread of content produced by artificial intelligence (AI). In addition, with the release of ChatGPT, virtually everyone can now create naturally sounding text on any topic. To optimize future use and understand how humans interact with these technologies, it is essential to capture people’s attitudes and beliefs. However, research on ATG perception is lacking. Based on two representative surveys (March 2022: n1 = 1028; July 2023: n2 = 1013), we aimed to examine the German population’s concepts of and attitudes toward AI authorship. The results revealed a preference for human authorship across a wide range of topics and a lack of knowledge concerning the function, data sources, and responsibilities of ATG. Using multiple regression analysis with k-fold cross-validation, we identified people’s attitude toward using ATG, performance expectancy, general attitudes toward AI, and lay attitude toward ChatGPT and ATG as significant predictors of the intention to read AI-written texts in the future. Despite the release of ChatGPT, we observed stability across most variables and minor differences between the two survey points regarding concepts about ATG. We discuss the findings against the backdrop of the ever-increasing availability of automated content and the need for an intensive societal debate about its chances and limitations.
Visual Field Restriction in the Recognition of Basic Facial Expressions: A Combined Eye Tracking and Gaze Contingency Study
Authors: Urtado Melina Boratto , Rodrigues Rafael Delalibera , Fukusima Sergio Sheiji
Published: April 2024

Uncertainties and discrepant results in identifying crucial areas for emotional facial expression recognition may stem from the eye tracking data analysis methods used. Many studies employ parameters of analysis that predominantly prioritize the examination of the foveal vision angle, ignoring the potential influences of simultaneous parafoveal and peripheral information. To explore the possible underlying causes of these discrepancies, we investigated the role of the visual field aperture in emotional facial expression recognition with 163 volunteers randomly assigned to three groups: no visual restriction (NVR), parafoveal and foveal vision (PFFV), and foveal vision (FV). Employing eye tracking and gaze contingency, we collected visual inspection and judgment data over 30 frontal face images, equally distributed among five emotions. Raw eye tracking data underwent Eye Movements Metrics and Visualizations (EyeMMV) processing. Accordingly, the visual inspection time, number of fixations, and fixation duration increased with the visual field restriction. Nevertheless, the accuracy showed significant differences among the NVR/FV and PFFV/FV groups, despite there being no difference in NVR/PFFV. The findings underscore the impact of specific visual field areas on facial expression recognition, highlighting the importance of parafoveal vision. The results suggest that eye tracking data analysis methods should incorporate projection angles extending to at least the parafoveal level.
The Properties of Magnesium Silicate Hydrate Prepared from the Magnesium Silicate Minerals in the Earth’s Crust
Authors: Song Qiang , He Qian , Nie Jiao , Song Tiantian , Zhou Hong , Hu Yaru , Chen Yanxin , Deng Yang , Cheng Fuan
Published: April 2024

In order to explore a wider range and lower cost of raw materials for the preparation of magnesium silicate hydrate (M-S-H), an acid-leaching method was employed to extract and separate high-purity magnesium hydroxide (Mg(OH)2) with a purity higher than 97% and amorphous silica with a purity higher than 90% from four types of natural silicate minerals (serpentine, peridotite, zeolite, and montmorillonite). These two intermediate products, which are amorphous silica and magnesium hydroxide, were used to prepare M-S-H, and the influence of curing at two temperatures, 50 °C and 80 °C, on the properties of M-S-H was investigated. The results showed that with the increase in curing temperature, the bound water content, tetrahedral polymerization degree, and Mg(OH)2 content increased. There was a good correlation between the increase in strength and the bound water content of M-S-H. This work provides a possible technological route for expanding the raw materials for preparing magnesium silicate hydrate cementitious materials and utilizing the abundant magnesium silicate minerals in the Earth’s crust.
Research on Positioning and Simulation Method for Autonomous Mobile Construction Platform
Authors: Shi Xinyu , Wang Chaoran , Phillips Tyson Keen , Sun Chengpeng , Zhou Haining , Zhao Wenxuan , Cui Weijiu , Wan Da
Published: April 2024

In the architecture, engineering, and construction (AEC) industry, the positioning technology for a mobile construction platform (MCP) is critical to achieve on-site, continuous, large-scale construction. During construction, MCP movement and construction actions seldom occur simultaneously. Therefore, this paper categorizes the MCP into stationary and moving states for positioning studies, respectively. When the platform is stationary, it is positioned using an improved ultra-wideband (UWB) sensor. When the platform is in motion, a single UWB positioning technique cannot meet the required accuracy for positioning, and fusion positioning using both UWB and an inertial measurement unit (IMU) is considered. The experimental results show that compared with only UWB positioning, the improved UWB positioning algorithm improves the positioning accuracy by 53% in the stationary state, and the fused UWB/IMU positioning improves the positioning accuracy by 46% in the moving state. As a result, the positioning accuracy of the MCP is significantly improved regardless of whether it is in a stationary or moving state. Furthermore, this paper integrates the positioning technique with the robotic arm construction technique to successfully simulate an on-site continuous construction of a wooden cabin, which provides the potential for large-scale continuous construction in real-world scenarios in the future.
Multiplex Digital Spatial Profiling in Breast Cancer Research: State-of-the-Art Technologies and Applications across the Translational Science Spectrum
Authors: Rossi Matilde , Radisky Derek C.
Published: April 2024

While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding cellular interactions and tissue dynamics. Multiplex digital spatial profiling (MDSP) technologies overcome this limitation by enabling the simultaneous analysis of transcriptome and proteome data within the intact spatial architecture of tissues. In breast cancer research, MDSP has emerged as a promising tool, revealing complex biological questions related to disease evolution, identifying biomarkers, and discovering drug targets. This review highlights the potential of MDSP to revolutionize clinical applications, ranging from risk assessment and diagnostics to prognostics, patient monitoring, and the customization of treatment strategies, including clinical trial guidance. We discuss the major MDSP techniques, their applications in breast cancer research, and their integration in clinical practice, addressing both their potential and current limitations. Emphasizing the strategic use of MDSP in risk stratification for women with benign breast disease, we also highlight its transformative potential in reshaping the landscape of breast cancer research and treatment.
Controversies in Endoscopic Ultrasound-Guided Biliary Drainage
Authors: Dietrich Christoph Frank , Arcidiacono Paolo Giorgio , Bhutani Manoop S. , Braden Barbara , Burmester Eike , Fusaroli Pietro , Hocke Michael , Ignee Andrè , Jenssen Christian , Al-Lehibi Abed , Aljahdli Emad , Napoléon Bertrand , Rimbas Mihai , Vanella Giuseppe
Published: April 2024

In this 14th document in a series of papers entitled “Controversies in Endoscopic Ultrasound” we discuss various aspects of EUS-guided biliary drainage that are debated in the literature and in practice. Endoscopic retrograde cholangiography is still the reference technique for therapeutic biliary access, but EUS-guided techniques for biliary access and drainage have developed into safe and highly effective alternative options. However, EUS-guided biliary drainage techniques are technically demanding procedures for which few training models are currently available. Different access routes require modifications to the basic technique and specific instruments. In experienced hands, percutaneous transhepatic cholangiodrainage is also a good alternative. Therefore, in this paper, we compare arguments for different options of biliary drainage and different technical modifications.
Interaction of Colorectal Neoplasm Risk Factors and Association with Metabolic Health Status Focusing on Normal Waist-to-Hip Ratio in Adults
Authors: Lin Ying-Chun , Ko Hung-Ju , Yu Lo-Yip , Chen Ming-Jen , Wang Horng-Yuan , Shih Shou-Chuan , Liu Chuan-Chuan , Kuo Yang-Che , Hu Kuang-Chun
Published: April 2024

Background: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. Methods: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. Results: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. Conclusions: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS.
Predictive and Prognostic Relevance of Tumor-Infiltrating Immune Cells: Tailoring Personalized Treatments against Different Cancer Types
Authors: Dakal Tikam Chand , George Nancy , Xu Caiming , Suravajhala Prashanth , Kumar Abhishek
Published: April 2024

TIICs are critical components of the TME and are used to estimate prognostic and treatment responses in many malignancies. TIICs in the tumor microenvironment are assessed and quantified by categorizing immune cells into three subtypes: CD66b+ tumor-associated neutrophils (TANs), FoxP3+ regulatory T cells (Tregs), and CD163+ tumor-associated macrophages (TAMs). In addition, many cancers have tumor-infiltrating M1 and M2 macrophages, neutrophils (Neu), CD4+ T cells (T-helper), CD8+ T cells (T-cytotoxic), eosinophils, and mast cells. A variety of clinical treatments have linked tumor immune cell infiltration (ICI) to immunotherapy receptivity and prognosis. To improve the therapeutic effectiveness of immune-modulating drugs in a wider cancer patient population, immune cells and their interactions in the TME must be better understood. This study examines the clinicopathological effects of TIICs in overcoming tumor-mediated immunosuppression to boost antitumor immune responses and improve cancer prognosis. We successfully analyzed the predictive and prognostic usefulness of TIICs alongside TMB and ICI scores to identify cancer’s varied immune landscapes. Traditionally, immune cell infiltration was quantified using flow cytometry, immunohistochemistry, gene set enrichment analysis (GSEA), CIBERSORT, ESTIMATE, and other platforms that use integrated immune gene sets from previously published studies. We have also thoroughly examined traditional limitations and newly created unsupervised clustering and deconvolution techniques (SpatialVizScore and ProTICS). These methods predict patient outcomes and treatment responses better. These models may also identify individuals who may benefit more from adjuvant or neoadjuvant treatment. Overall, we think that the significant contribution of TIICs in cancer will greatly benefit postoperative follow-up, therapy, interventions, and informed choices on customized cancer medicines.
Bone Marrow Adipose Tissue
Authors: Marinelli Busilacchi Elena , Morsia Erika , Poloni Antonella
Published: April 2024

Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes an essential element of the BM microenvironment that participates in homeostasis, influences bone health and bone remodeling, alters hematopoietic stem cell functions, contributes to the commitment of mesenchymal stem cells, provides effects to immune homeostasis and defense against infections, and participates in energy metabolism and inflammation. BMAT has emerged as a significant contributor to the development and progression of various diseases, shedding light on its complex relationship with health. Notably, BMAT has been implicated in metabolic disorders, hematological malignancies, and skeletal conditions. BMAT has been shown to support the proliferation of tumor cells in acute myeloid leukemia and niche adipocytes have been found to protect cancer cells against chemotherapy, contributing to treatment resistance. Moreover, BMAT’s impact on bone density and remodeling can lead to conditions like osteoporosis, where high levels of BMAT are inversely correlated with bone mineral density, increasing the risk of fractures. BMAT has also been associated with diabetes, obesity, and anorexia nervosa, with varying effects on individuals depending on their weight and health status. Understanding the interaction between adipocytes and different diseases may lead to new therapeutic strategies.
Patient-Derived Organoids Recapitulate Pathological Intrinsic and Phenotypic Features of Fibrous Dysplasia
Authors: Kim Ha-Young , Charton Clémentine , Shim Jung Hee , Lim So Young , Kim Jinho , Lee Sejoon , Ohn Jung Hun , Kim Baek Kyu , Heo Chan Yeong
Published: April 2024

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.
Tumor Microenvironment Modulates Invadopodia Activity of Non-Selected and Acid-Selected Pancreatic Cancer Cells and Its Sensitivity to Gemcitabine and C18-Gemcitabine
Authors: Carvalho Tiago M. A. , Audero Madelaine Magalì , Greco Maria Raffaella , Ardone Marilena , Maggi Teresa , Mallamaci Rosanna , Rolando Barbara , Arpicco Silvia , Ruffinatti Federico Alessandro , Pla Alessandra Fiorio , Prevarskaya Natalia , Koltai Tomas , Reshkin Stephan J. , Cardone Rosa Angela
Published: April 2024

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with high mortality due to early metastatic dissemination and high chemoresistance. All these factors are favored by its extracellular matrix (ECM)-rich microenvironment, which is also highly hypoxic and acidic. Gemcitabine (GEM) is still the first-line therapy in PDAC. However, it is quickly deaminated to its inactive metabolite. Several GEM prodrugs have emerged to improve its cytotoxicity. Here, we analyzed how the acidic/hypoxic tumor microenvironment (TME) affects the response of PDAC cell death and invadopodia-mediated ECM proteolysis to both GEM and its C18 prodrug. Methods: For this, two PDAC cell lines, PANC-1 and Mia PaCa-2 were adapted to pHe 6.6 or not for 1 month, grown as 3D organotypic cultures and exposed to either GEM or C18 in the presence and absence of acidosis and the hypoxia inducer, deferoxamine. Results: We found that C18 has higher cytotoxic and anti-invadopodia activity than GEM in all culture conditions and especially in acid and hypoxic environments. Conclusions: We propose C18 as a more effective approach to conventional GEM in developing new therapeutic strategies overcoming PDAC chemoresistance.
Precise Prediction of Long-Term Urinary Incontinence after Robot-Assisted Laparoscopic Radical Prostatectomy by Readily Accessible “Everyday” Diagnostics during Post-Surgical Hospitalization
Authors: Mohr Mirjam Naomi , Ploeger Hannah Maria , Leitsmann Marianne , Leitsmann Conrad , Gayer Fabian Alexander , Trojan Lutz , Reichert Mathias
Published: April 2024

Aim and Objectives: We aimed to test the predictive value of readily accessible and easily performed post-surgical “bedside tests” on their validity of long-term urinary incontinence (UI) (≥12 months) in patients following robot-assisted laparoscopic radical prostatectomy (RALP). Material and Methods: Patients undergoing RALP between July 2020 and March 2021 were prospectively included and subdivided into two groups based on their pad usage after 12 months (0 vs. ≥1 pad). After catheter removal, patients performed a 1 h pad test, documented the need for pad change in a micturition protocol and received post-voiding residual urine volume ultrasound. Univariate and multivariable analyses were used to demonstrate the predictive value of easily accessible tests applied after catheter removal for UI following RALP. Results: Of 109 patients, 47 (43%) had to use at least one pad (vs. 62 (57%) zero pads) after 12 months. Univariate testing showed a significant difference in urine loss between both groups evaluated by the 1 h pad test performed within 24 h after catheter removal (70% < 10 mL, vs. 30% ≥ 10 mL, p = 0.004) and in the need for pad change within the first 24 h after catheter removal (14% dry pads vs. 86% wet pads, p = 0.003). In multivariable analyses, the combination of both tests (synoptical incontinence score) could be confirmed as an independent predictor for UI after 12 months (p = 0.011). Conclusions: Readily accessible “everyday” diagnostics (pad test/change of pads after catheter removal) following RALP seem to be associated with a higher rate of long-term UI. This finding is crucial since patients with a potentially higher need for patient education and counselling can be identified using these readily accessible tests. This could lead to a higher patient satisfaction and improved outcomes.
Blood Count and Renal Functionality Assessments in the Emergency Section Disclose Morbidity and Mortality in Omicron COVID-19 Patients: A Retrospective Study
Authors: Rusi Eqrem , Pennacchia Fiorenza , Ruqa Wael Abu , Zingaropoli Maria Antonella , Pasculli Patrizia , Talarico Giuseppina , Bruno Giuseppe , Barbato Christian , Minni Antonio , Tarani Luigi , Galardo Gioacchino , Pugliese Francesco , Lucarelli Marco , Ciardi Maria Rosa , Meucci Luigi , Ferraguti Giampiero , Fiore Marco
Published: April 2024

Background: SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Even though we are no longer in a pandemic situation, people are still getting infected, some of them need hospitalization and a few of them die. Methods: We conducted a retrospective study including 445 patients who accessed the Emergency Section of Policlinico Umberto I, Rome, Italy, where they had routine blood exams. In this study, we focused on the complete blood count, serum creatinine and azotemia. The data were analyzed using ANOVA, Spearman correlation and ROC analyses. They were divided into four groups based on their clinical outcomes: (1) the emergency group (patients who had mild forms and were quickly discharged); (2) the hospital ward group (patients who were admitted to the emergency section and were then hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients who required intensive assistance after the admission in the emergency section); (4) the deceased group (patients who had a fatal outcome after admission to the emergency section). Results: We found significant changes for creatinine, azotemia, hematocrit, mean corpuscular hemoglobin concentration, basophils, monocytes, red blood cell distribution width, hemoglobin, hematocrit and red blood cell numbers using ANOVA according to their clinical outcomes, particularly for the deceased group. Also, we found linear correlations of clinical outcomes with eosinophils, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, lymphocyte, neutrophil, platelet and red blood cell number and red blood cell distribution width. Conclusions: This study discloses an early association between “classical” routine blood biomarkers and the severity of clinical outcomes in Omicron patients.
The Contribution of Genetic Testing in Optimizing Therapy for Patients with Recurrent Depressive Disorder
Authors: Platona Rita Ioana , Voiță-Mekeres Florica , Tudoran Cristina , Tudoran Mariana , Enătescu Virgil Radu
Published: April 2024

(1) Background: The aim of this study was to analyze the impact of pharmacogenetic-guided antidepressant therapy on the 12-month evolution of the intensity of depressive symptoms in patients with recurrent depressive disorder (RDD) in comparison to a control group of depressive subjects who were treated conventionally. (2) Methods: This prospective longitudinal study was conducted between 2019 and 2022, and the patients were evaluated by employing the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impressions Scale: Severity and Improvement. We followed them up at 1, 3, 6, and 12 months. (3) Results: Of the 76 patients with RDD, 37 were tested genetically (Group A) and 39 were not (Group B). Although the patients from Group A had statistically significantly more severe MDD at baseline than those from Group B (p < 0.001), by adjusting their therapy according to the genetic testing, they had a progressive and more substantial reduction in the severity of RDD symptoms [F = 74.334; η2 = 0.674; p < 0.001], indicating a substantial association with the results provided by the genetic testing (67.4%). (4) Conclusions: In patients with RDD and a poor response to antidepressant therapy, pharmacogenetic testing allows for treatment adjustment, resulting in a constant and superior reduction in the intensity of depression and anxiety symptoms.
Design and Application of Rich Bottom Layer Mixtures
Authors: Wei Zhiqiang , Abdukadir Abduhaibir , Zhao Xiangqing , Cui Honghai , Yi Junyan
Published: April 2024

This study aims to summarize design indexes for rich bottom layer mixtures (RBLMs) and design asphalt mixtures with superior performance to reduce reflective cracks and fatigue cracking resulting from semi-rigid base cracking in the asphalt layer. First, this study synthesizes the research results about RBLMs and introduces the related design indexes. After that, using ABAQUS 6.13, finite element analysis was performed to analyze the change in bottom stress when the base cracked and the interlayer bond weakened. SBS-modified asphalt mixtures (SMMs) and composite-modified asphalt mixtures (CMMs) were subsequently developed as RBLMs utilizing the Marshall test method and applied on a test road. The research findings reveal that design indexes for RBLMs include a volume of air voids (VVs) within the range of 2.0%–3.0%, a maximum flexural strain exceeding 3500 με, and a dynamic stability surpassing 1000 cycles/mm. Both mixtures satisfy the design requirements, with the CMM demonstrating superior performance and offering promising application prospects. Future research endeavors will concentrate on prolonged monitoring of the test section to authenticate the effectiveness of an RBL in practical road applications.