bluuebunny/crossref_metadata_2025 huggingface dataset:
Additive Manufacturing Oriented Parametric Design Automation of Adaptive Joint System for an Irregular Form Gridshell Structure
Authors: Ahn Jin-Ho , Ham Nam-Hyuk , Kim Ju-Hyung , Kim Jae-Jun
Published: November 2024

In architectural engineering, triangular tessellation using polygon mesh topology is one of the commonly used computational geometric approaches to simplify a free curved building façade into flat triangular facets and their subsequent straight edges. In such a façade system, exterior panels are supported by a network of profiles that correspond to their edges hidden behind the panels at an offset distance. A group of profiles, derived from the edges common to a node point of tessellated panels (i.e., the outermost panels enveloping the building), may dislocate from each other when offset from their original locations due to non-coplanar alignment and unique offset directions and distances. This dislocation problem gives rise to geometric complications in nodal connector design in addition to varying in the connected profile count and orientations. Design considerations regarding the effects of ’offset vertex dislocation’ (i.e., the dislocation of the edges when it offsets from the original topology due to incoherent normal direction) should incorporate proper variables in the correct sequence based on a fundamental understanding that causes the dislocation problem. However, it is very often these topological problems pertaining to offset that are neglected, leading to subsequent design flaws. Such oversights diminish the inherent strengths of DfMA (design for manufacture and assembly) and design automation. This study develops a computational mathematical approach aimed at addressing the geometric complexities in nodal connector design. It focuses on two main areas: the precise positioning of substructure profiles essential for the design and a design automation approach that minimizes the length of the nodal connector arms to enhance 3D printing productivity. A life-scale proof-of-concept structure based on an automated parametric design process that implements the research findings demonstrates the application, incorporating 3D-printed PA12 (Polyamide-12) nodal connectors.
Negative Selection Algorithm for Unsupervised Anomaly Detection
Authors: Bereta Michał
Published: November 2024

In this work, we present a modification of the well-known Negative Selection Algorithm (NSA), inspired by the process of T-cell generation in the immune system. The approach employs spherical detectors and was initially developed in the context of semi-supervised anomaly detection. The novelty of this work lies in proposing an adapted version of the NSA for unsupervised anomaly detection. The goal is to develop a method that can be applied to datasets that may not only represent self-data but also contain a small percentage of anomalies, which must be detected without prior knowledge of their locations. The proposed unsupervised algorithm leverages neighborhood sampling and ensemble methods to enhance its performance. We conducted comparative tests with 11 other algorithms across 17 datasets with varying characteristics. The results demonstrate that the proposed algorithm is competitive. The proposed algorithm performs well across multiple metrics, including accuracy, AUC, precision, recall, F1 score, Cohen’s kappa, and Matthews correlation coefficient. It consistently ranks among the top algorithms for recall, indicating its effectiveness in scenarios where detecting all existing anomalies is critical, even at the expense of some increase in false positives. Further research is possible and may focus on exploring normalization procedures, improving threshold automation, and extending the method for more detailed anomaly confidence assessments.
Microseismic Electronic Fencing for Monitoring of Transboundary Mining in Mines
Authors: Yang Jianbiao , Lu Guangyin , Li Lei , Zhang Dazhou
Published: November 2024

Mine transboundary mining has been occurring frequently in recent years, and this illegal behavior has brought great potential danger to mine safety while also causing greater losses of state-owned assets. However, the current method of monitoring transboundary mining is still mainly based on underground verification by supervisors, which is far from meeting the demand for supervision. Microseismic monitoring technology is effective for monitoring transboundary mining due to its ability to locate vibration signals. For mine transboundary mining monitoring, this paper proposes a microseismic electronic fence method focusing on mine boundary locating, which differs from the routine microseismic monitoring used in mining operations. This method focuses its key monitoring area on the mine boundary. The deployment mode, number of sensors, and localization theory are analyzed, and numerical simulation and field measurement data analysis results show that the microseismic electronic fence method can achieve a localization accuracy of 15–20 m for underground microseismic events in the vicinity of mine boundaries, which can be effectively applied to the monitoring of transboundary mining activities.
A Consensus Framework for Evaluating Dispute Resolution Alternatives in International Law Using an Interval-Valued Type-2 Fuzzy TOPSIS Approach
Authors: Yilmaz Ibrahim , Ecemis Yilmaz Hatice Kubra
Published: November 2024

This research is motivated by the arbitrary nature of decision-making environments and the dynamic changes in decision patterns, particularly in international dispute resolution. These challenges introduce uncertainties that could be effectively managed by fuzzy logic, which provides a robust framework for evaluating alternatives under multiple criteria. In this study, an Interval-Valued Type-2 Fuzzy TOPSIS approach is proposed to assess various dispute resolution methods, including negotiation, good offices, mediation, international inquiry, conciliation, international organization, arbitration, and international jurisdiction. Common criteria are determined by examining academic literature and by interviewing relevant experts.—cost-efficiency, duration, impartiality, binding nature, and generalizability are considered essential in determining the best resolution method. The proposed method allows for a nuanced evaluation by incorporating both primary and secondary levels of uncertainty, enabling decision-makers to determine the best alternative solution more reliably. This method’s application extends not only to the international law field but also to industrial engineering, where complex, uncertain decision environments require similarly sophisticated multicriteria decision-making tools. By systematically analyzing these resolution methods, this study aims to provide a structured, quantifiable approach that enhances the decision-making process for both international legal practitioners and engineers working with uncertain and dynamic systems. The results of this study ultimately contribute to improved decision-making outcomes and greater efficiency in multidisciplinary problem solving. The assessments of experts in international law, international relations, and political science in their respective fields of expertise have been gathered to form a consensus. This study contributes to the literature as it is the pioneering application of fuzzy multicriteria decision-making techniques in the field of international law. The results of this study imply that the best option from the different decision-maker evaluations is international jurisdiction. Consequently, the utilization of multicriteria decision-making tools can result in more informed and effective decisions in complex and uncertain situations, which is advantageous to both legal practitioners and engineers. Additionally, incorporating different disciplines can help streamline the decision-making process and improve overall efficiency in solving multidisciplinary problems.
COVID-19 Lung Injury: Unique and Familiar Aspects of Pathophysiology
Authors: Hall Stefan , Berger Geraint , Lehmann Christian
Published: November 2024

Acute lung injury (ALI), diagnosed clinically as acute respiratory distress syndrome (ARDS), refers to a spectrum of acute inflammatory processes culminating in increased permeability of the pulmonary alveolar–capillary barrier and impaired gas exchange. The pandemic caused by the novel coronavirus, SARS-CoV-2, has raised questions as to the similarities and differences between COVID-19 lung injury and ALI of other etiologies. This review summarizes current knowledge regarding the pathophysiology of ALI and COVID-19 lung injury and draws comparisons between the latter and other infectious etiologies of ALI. Indeed, severe COVID-19 is characterized by a unique array of disease mechanisms including suppression of interferon responses, widespread inflammasome activation, altered leukocyte phenotypes, and hyperactive thrombotic activity. Moreover, these mechanisms manifest as a unique clinical progression, which further differentiates COVID-19 from other viral respiratory pathogens such as SARS, MERS, and influenza. These unique features of COVID-19 pathophysiology bear important implications for current and future therapeutic strategies.
Monitoring Perishable Commodities Using Cellular IoT: An Intelligent Real-Time Conditions Tracker Design
Authors: Garrido-López Javier , Jiménez-Buendía Manuel , Toledo-Moreo Ana , Giménez-Gallego Jaime , Torres-Sánchez Roque
Published: November 2024

Perishable product losses can occur throughout postharvest handling. Proper monitoring of key environmental conditions during this period is essential for predicting quality losses throughout their shelf life. This paper presents the design and testing of a portable and compact datalogger for the real-time monitoring of environmental conditions throughout the food supply chain. The device developed incorporates high-precision sensors to measure temperature, relative humidity, CO2 concentration, luminosity and vibrations, as well as wireless communication capabilities for data transmission, simplifying real-time monitoring over existing multi-component systems while keeping costs affordable. Strategies to optimize power consumption allow a month of battery life, being able to cover entire periods of transport and storage, according to the results of the autonomy test performed on the device. The datalogger uses NB-IoT and relies on other wireless communication protocols if not available to send sensor data to a cloud platform. Comparative testing with commercial dataloggers has been carried out to verify correct device measurements, and field testing has validated successful real-time data transmission along an entire refrigerated transport route. The functionality and autonomy of the proposed device meet the needs of live remote monitoring to help reduce food losses.
Reflecting on City Governmental Responses to COVID-19: Focus on Design Justice
Authors: Kim Joongsub , Vogel Stephen
Published: November 2024

In the early stages of the COVID-19 pandemic and the resultant stay-at-home mandates, local governments in some cities in the United States implemented programs in response to the pandemic. This article focuses on Slow Streets, which were several programs implemented in eleven cities (Los Angeles, Oakland, San Francisco, Seattle, Portland, Denver, Chicago, Minneapolis, Detroit, Boston, and New York) in the United States. The programs were intended to keep people healthy by providing temporary public spaces on residential roads where residents were allowed to exercise and socialize. Some practitioners characterized the programs as tactical urbanism or tactical placemaking and as agile responses to the public health crisis. The programs deserve a critical reflection, considering their potential impact on community health and the limited amount of the literature on the program in terms of design justice, which is an approach to design that prioritizes marginalized communities and challenges their structural inequality. This reflective study attempts to fill that gap in the literature of architecture and urban design. This article aims to examine whether the Slow Streets programs promoted design justice. To address that aim, we propose a social justice framework to evaluate the program, because social justice is essential to design justice. Data from publicly available information online about the eleven cities’ Slow Streets programs, interviews, surveys, focus groups, and the interdisciplinary literature support the qualitative research. The study outcomes suggest that the Slow Streets program had limited success because their attention to the priorities of underserved populations was ineffective. We argue that while the programs provided a timely response to the pandemic, the programs did not adequately address the vulnerability of low-income communities of color due to the limited consideration of design justice. Building on the lessons from social justice and human geography, the article concludes with recommendations for future practices including place-cultivating and human geography-informed design to better serve vulnerable communities of color.
Interactions Between a High-Intensity Wildfire and an Atmospheric Hydraulic Jump in the Case of the 2023 Lahaina Fire
Authors: Ehrke Clifford , Farguell Angel , Kochanski Adam K.
Published: November 2024

On 8 August 2023, a grass fire that started in the city of Lahaina, Hawai’i, grew into the deadliest wildfire in the United States since 1918. This wildfire offers a unique opportunity to explore the impact of high heat output on an atmospheric hydraulic jump and a downslope wind event. We conducted two WRF-SFIRE simulations to investigate these effects: one incorporating fire–atmosphere feedback and the other without it. Our findings revealed that, in the uncoupled simulation, the hydraulic jump moved inland significantly earlier than in the coupled simulation. This altered the wind pattern near the fire front in the uncoupled simulation, accelerating its lateral spread. The results suggest that fire–atmosphere interactions and their influence on near-fire circulation may be more intricate than previously understood. Specifically, while fire-induced wind acceleration is often linked to enhanced fire spread, this study highlights that, in cases where the lateral fire spread is dominant, fire-induced circulation may reduce cross-flank flow and inhibit the fire growth.
Studying the Impact of LULC Correspondence Between Landsat 8 and Spot 7 Data on Land Surface Temperature Estimation
Authors: Miky Yehia
Published: November 2024

Information about land surface temperature (LST) plays a crucial role in environmental studies, as it provides essential data for understanding climate patterns, assessing ecosystem health, and predicting environmental changes. Understanding the relationship between land cover types and LST is crucial across all disciplines that deal with LST data. It helps researchers identify trends in global warming, heatwaves, and cooling effects, which can influence biodiversity, agriculture, and water resources. The accuracy of LST calculations heavily depends on the quality of the data used. However, most satellite thermal data used for LST estimations are in coarse spatial resolution. This study aims to explore the complex interaction between land cover types, considering factors such as proportion and neighboring effects, and LST recalculation by integrating the estimated LST from Landsat thermal band and Spot imagery classification. A machine learning model was employed to quantify the contribution of each Spot pixel to the LST estimated from TIRS data, classifying it as either heating or cooling. The Al Morjan and Al Hamra districts in Jeddah, Saudi Arabia, were used as case studies. The results showed that Spot images achieved a classification accuracy of over 95%, whereas Landsat images did not exceed 77%. The average heating and cooling factors from neighboring pixels were 1.06 and 0.96, respectively. The study demonstrates the improved spatial distribution of LST, with overall temperature increases across all land cover classes. The findings of this study could aid in identifying environmental imbalances and developing effective solutions.
Smoothed Weighted Quantile Regression for Censored Data in Survival Analysis
Authors: Cai Kaida , Liu Hanwen , Fu Wenzhi , Zhao Xin
Published: November 2024

In this study, we propose a smoothed weighted quantile regression (SWQR), which combines convolution smoothing with a weighted framework to address the limitations. By smoothing the non-differentiable quantile regression loss function, SWQR can improve computational efficiency and allow for more stable model estimation in complex datasets. We construct an efficient optimization process based on gradient-based algorithms by introducing weight refinement and iterative parameter estimation methods to minimize the smoothed weighted quantile regression loss function. In the simulation studies, we compare the proposed method with two existing methods, including martingale-based quantile regression (MartingaleQR) and weighted quantile regression (WeightedQR). The results emphasize the superior computational efficiency of SWQR, outperforming other methods, particularly WeightedQR, by requiring significantly less runtime, especially in settings with large sample sizes. Additionally, SWQR maintains robust performance, achieving competitive accuracy and handling the challenges of right censoring effectively, particularly at higher quantiles. We further illustrate the proposed method using a real dataset on primary biliary cirrhosis, where it exhibits stable coefficient estimates and robust performance across quantile levels with different censoring rates. These findings highlight the potential of SWQR as a flexible and robust method for analyzing censored data in survival analysis, particularly in scenarios where computational efficiency is a key concern.
Existence and Uniqueness of Second-Order Impulsive Delay Differential Systems
Authors: Zhou Yingxia , Li Mengmeng
Published: November 2024

In this paper, we study the existence and uniqueness of second-order impulsive delay differential systems. Firstly, we define cosine-type and sine-type delay matrix functions, which are used to derive the solutions of the impulsive delay differential systems. Secondly, based on the Schauder and Banach fixed-point theorems, we establish sufficient conditions that guarantee the existence and uniqueness of solutions to nonlinear impulsive delay differential systems. Finally, several examples are given to illustrate our theoretical results.
Effect of Thermovinification Temperature on Phenolic Compounds and Colour of Syrah Wine
Authors: Silva Islaine Santos , Barros Ana Paula André , Correa Luiz Claudio , de Souza Carolina Oliveira , Biasoto Aline Camarão Telles
Published: November 2024

Background: Thermovinification is a non-conventional winemaking practice that replaces the traditional method of grape maceration. Methods: This study evaluated the influence of thermovinification temperature on the quality of Syrah wines. The treatments included traditional winemaking with 7 days of maceration during alcoholic fermentation at 23 °C (TW—control); and thermovinification for 2 h at 55 °C (TV55), 65 °C (TV65), and 75 °C (TV75). The red wines were made through microvinification (10-litre glass). Phenolic compounds (n = 26) were quantified by high-performance liquid chromatography and a colour analysis using the CIELab/CIEL*C*h systems and a sensory analysis was conducted to evaluate the acceptability of the thermovinified wine. Results: The results indicate that thermovinification increased the content of bioactive compounds and intensified the colour of the wine, reducing L* and a*. However, the content of phenolic acids decreased, except for trans-caftaric acid, which was approximately 50 times higher. A higher temperature of thermovinification (75 °C) promoted the degradation of all anthocyanins. Among flavonols, kaempferol-3-O-glucoside, quercetin-3-β-D-glucoside, and isorhamnetin-3-O-glucoside were higher in TV65 and TV75 wines. Greater amounts of stilbenes were quantified in TV65. Among the flavan-3-ols, TV75 stood out, especially for (+)-catechin, (−)-epicatechin, procyanidin A2, and procyanidin B1. Conclusions: The thermovinification at 65 °C is optimal for minimising anthocyanin degradation and improving Syrah wine quality.
Oocytes Quality Assessment—The Current Insight: A Systematic Review
Authors: Ahmad Mohd Faizal , Elias Marjanu Hikmah , Mat Jin Norazilah , Abu Muhammad Azrai , Syafruddin Saiful Effendi , Zainuddin Ani Amelia , Suzuki Nao , Abdul Karim Abdul Kadir
Published: November 2024

An overall in vitro fertilization (IVF) outcome is dynamic. Good oocyte quality is important for achieving a better IVF pregnancy. Various methods have been used for OQ assessment (OQA). However, due to inconclusive evidence, one method’s superiority has not been proposed over others. Thus, OQA should be consolidated based on the current evidence for this matter. Our study aims to summarize the current OQA used and compare their recommended methods. Our results revealed that the optimal OQA for cost-effectiveness and clinical implementation is still via morphological assessment. The current method most opted for is total oocyte scoring. Although other methods—follicular fluid evaluation, mitochondria spindle assessment, or live zona imaging—can be applied with better precision, due to cost, additional tools, and expertise, and they should cater to research purposes and selected centers. Our results added value as a current strategy for optimizing OQA in IVF practice, aiming at cost-effectiveness and reproducibility for better clinical implementation.
Role of Nicotinamide in the Pathogenesis of Actinic Keratosis: Implications for NAD+/SIRT1 Pathway
Authors: Belardi Riccardo , Pacifici Francesca , Cosio Terenzio , Lambiase Sara , Shumak Ruslana Gaeta , Artosi Fabio , Rivieccio Antonia , Cavalloro Danilo , Dellambra Elena , Bianchi Luca , Della-Morte David , Campione Elena
Published: November 2024

Actinic keratosis (AK) is a precursor to invasive squamous cell carcinoma, making early diagnosis and treatment essential to prevent progression. Among available therapeutic options, nicotinamide (NAM) has shown potential in reducing AK progression. NAM is a precursor of nicotinamide adenine dinucleotide (NAD+), which activates sirtuin (SIRT)1, a protein with anti-cancer properties. Although the role of SIRT1 in AK is still debated, no data currently exist on the systemic modulation of this protein in AK. Therefore, this study aims to evaluate whether NAM, by increasing serum NAD+ levels, may promote SIRT1 activation in peripheral blood mononuclear cells (PBMCs) in AK patients. Thirty patients were enrolled and treated with NAM for 24 months. Hematological, biochemical, and skin condition assessments were conducted, alongside the measurement of SIRT1 and NAD+ levels. A decrease in basophils, monocytes, total cholesterol, and blood glucose levels was observed in the study group, along with a reduction in AK lesions. Notably, NAM treatment significantly enhanced serum NAD+ levels, and nuclear SIRT1 activity in PBMCs. In conclusion, NAM administration significantly reduced AK progression in a NAD+/SIRT1-dependent manner, supporting its role as a chemopreventive agent in AK management.
NALCN Promoter Methylation as a Biomarker for Metastatic Risk in a Cohort of Non-Small Cell Lung Cancer Patients
Authors: Thanou Eleni , Lontra Dora , Balgouranidou Ioanna , Efthimiadou Eleni , Delipetrou Alexandra , Tsaroucha Emilia , Theodosiou Maria , Georgoulias Vassilis , Kotsakis Athanasios , Lianidou Evi , Markou Athina
Published: November 2024

Liquid biopsy enables real-time monitoring of tumor development and response to therapy through the analysis of CTCs and ctDNA. NALCN is a sodium leak channel that is frequently involved in tumor evolution and immunity and acts as a tumor suppressor. Deletion of NALCN has been shown to increase cancer metastasis and the number of CTCs in peripheral blood. In this study, we investigated for the first time NALCN promoter methylation in (a) Aza-treated cell lines (A549, TE671, BT20, and MDA-MB-468), (b) paired NSCLC tissues (n = 22), and (c) plasma cell-free DNA (ctDNA) from patients with NSCLC (early stage n = 39, metastatic n = 39) and DNA from 10 healthy donors (HD) using a newly developed highly specific and sensitive real-time MSP method. Treatment with 5′-aza-dC induced the expression of NALCN only in the A549 cell line, suggesting that DNA methylation regulates its expression in certain cancers. The mRNA expression levels of NALCN were quantified in non-small cell lung cancer (NSCLC) and adjacent non-cancerous tissues, and it was found to be underexpressed in 54.5% of tumor tissues, with significantly higher expression in recurrence-free patients (p = 0.009) than in patients who relapsed. The NALCN methylation level was not statisticallysignificantlycorrelated with the corresponding expression (p = 0.439), while Kaplan–Meier analysis showed an association between NALCN promoter hypermethylation and worse disease-free intervals (DFIs) (p = 0.017). Evaluation of NALCN methylation in ctDNA revealed that it was detected in 5.1% of early and 10.2% of advanced cases. Our results strongly suggest that epigenetic inactivation of NALCN may be a predictor of metastasis in NSCLC. Our results should be validated in further studies based on a larger patient cohort to further investigate whether DNA methylation of the NALCN promoter could serve as a potential prognostic DNA methylation biomarker and predictor of metastasis in NSCLC.
Molecular Mechanisms Underlying Initiation and Activation of Autophagy
Authors: Wei Zhixiao , Hu Xiao , Wu Yumeng , Zhou Liming , Zhao Manhan , Lin Qiong
Published: November 2024

Autophagy is an important catabolic process to maintain cellular homeostasis and antagonize cellular stresses. The initiation and activation are two of the most important aspects of the autophagic process. This review focuses on mechanisms underlying autophagy initiation and activation and signaling pathways regulating the activation of autophagy found in recent years. These findings include autophagy initiation by liquid–liquid phase separation (LLPS), autophagy initiation in the endoplasmic reticulum (ER) and Golgi apparatus, and the signaling pathways mediated by the ULK1 complex, the mTOR complex, the AMPK complex, and the PI3KC3 complex. Through the review, we attempt to present current research progress in autophagy regulation and forward our understanding of the regulatory mechanisms and signaling pathways of autophagy initiation and activation.
Comparative Effects of GLP-1 and GLP-2 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation
Authors: Ali Asif , Khan Dawood , Dubey Vaibhav , Tarasov Andrei I. , Flatt Peter R. , Irwin Nigel
Published: November 2024

Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are related intestinal L-cell derived secretory products. GLP-1 has been extensively studied in terms of its influence on metabolism, but less attention has been devoted to GLP-2 in this regard. The current study compares the effects of these proglucagon-derived peptides on pancreatic beta-cell function, as well as on glucose tolerance and appetite. The insulin secretory effects of GLP-1 and GLP-2 (10−12–10−6 M) were investigated in BRIN-BD11 beta-cells as well as isolated mouse islets, with the impact of test peptides (10 nM) on real-time cytosolic cAMP levels further evaluated in mouse islets. The impact of both peptides (10−8–10−6 M) on beta-cell growth and survival was also studied in BRIN BD11 cells. Acute in vivo (peptides administered at 25 nmol/kg) glucose homeostatic and appetite suppressive actions were then examined in healthy mice. GLP-1, but not GLP-2, concentration dependently augmented insulin secretion from BRIN-BD11 cells, with similar observations made in isolated murine islets. In addition, GLP-1 substantially increased [cAMP]cyt in islet cells and was significantly more prominent than GLP-2 in this regard. Both GLP-1 and GLP-2 promoted beta-cell proliferation and protected against cytokine-induced apoptosis. In overnight fasted healthy mice, as well as mice trained to eat for 3 h per day, the administration of GLP-1 or GLP-2 suppressed appetite. When injected conjointly with glucose, both peptides improved glucose disposal, which was associated with enhanced glucose-stimulated insulin secretion by GLP-1, but not GLP-2. To conclude, the impact of GLP-1 and GLP-2 on insulin secretion is divergent, but the effects of beta-cell signaling and overall health are similar. Moreover, the peripheral administration of either hormone in rodents results in comparable positive effects on blood glucose levels and appetite.
In Vitro Models of Cardiovascular Disease: Embryoid Bodies, Organoids and Everything in Between
Authors: Stougiannou Theodora M. , Christodoulou Konstantinos C. , Karangelis Dimos
Published: November 2024

Cardiovascular disease comprises a group of disorders affecting or originating within tissues and organs of the cardiovascular system; most, if not all, will eventually result in cardiomyocyte dysfunction or death, negatively impacting cardiac function. Effective models of cardiac disease are thus important for understanding crucial aspects of disease progression, while recent advancements in stem cell biology have allowed for the use of stem cell populations to derive such models. These include three-dimensional (3D) models such as stem cell-based models of embryos (SCME) as well as organoids, many of which are frequently derived from embryoid bodies (EB). Not only can they recapitulate 3D form and function, but the developmental programs governing the self-organization of cell populations into more complex tissues as well. Many different organoids and SCME constructs have been generated in recent years to recreate cardiac tissue and the complex developmental programs that give rise to its cellular composition and unique tissue morphology. It is thus the purpose of this narrative literature review to describe and summarize many of the recently derived cardiac organoid models as well as their use for the recapitulation of genetic and acquired disease. Owing to the cellular composition of the models examined, this review will focus on disease and tissue injury associated with embryonic/fetal tissues.
The Functional Role and Prognostic Significance of TIM-3 Expression on NK Cells in the Diagnostic Bone Marrows in Acute Myeloid Leukemia
Authors: Sun Kai , Shi Zong-Yan , Xie Dai-Hong , Wang Ya-Zhe , Jiang Hao , Jiang Qian , Huang Xiao-Jun , Qin Ya-Zhen
Published: November 2024

Background: Compared to other immune checkpoint molecules, T cell immunoglobulin domain and mucin domain-3 (TIM-3) is highly expressed on natural killer (NK) cells, but its functional role and prognostic significance in acute myeloid leukemia (AML) remains unclear. This study aims to evaluate the role of TIM-3 expression on the cytotoxic and killing capacity of NK cells and its prognostic significance in AML. Methods: AML public single-cell RNA sequencing (scRNAseq) data were used to analyze the correlation of transcript levels between HAVCR2 (encoding TIM-3) and cytotoxic molecules in NK cells. NK cells from the bone marrows of seven newly diagnosed AML patients and five healthy donors (HDs) were stimulated in vitro and cell-killing activity was evaluated. A total of one hundred and five newly diagnosed adult AML patients and seven HDs were tested the expression of TIM-3 and cytotoxic molecules on the bone marrow NK cells by multi-parameter flow cytometry (MFC). Results: Both scRNAseq and MFC analysis demonstrated that TIM-3 expression on NK cells was positively related to the levels of perforin (PFP) and granzyme B (GZMB) (all p < 0.05) in AML. It was PFP and GZMB but not the TIM-3 level that was related to NK-cell-killing activity against K562 cells (p = 0.027, 0.042 and 0.55). A high frequency of TIM-3+ NK cells predicted poorer relapse-free survival (RFS) and event-free survival (EFS) (p = 0.013 and 0.0074), but was not an independent prognostic factor, whereas low GZMB levels in TIM-3+ NK cells independently predicted poorer RFS (p = 0.0032). Conclusions: TIM-3 expression on NK cells is positively related to PFP and GZMB levels but has no relation to cell-killing activity in AML, and low GZMB levels in TIM-3+ NK cells in the diagnostic bone marrows predicts poor outcomes. This study lays a theoretical foundation for the clinical application of immune checkpoint inhibitor treatment.
Mitochondrial Dysfunction in Atrial Fibrillation: The Need for a Strong Pharmacological Approach
Authors: Mauriello Alfredo , Correra Adriana , Molinari Riccardo , Del Vecchio Gerardo Elia , Tessitore Viviana , D’Andrea Antonello , Russo Vincenzo
Published: November 2024

Despite great progress in treating atrial fibrillation (AF), especially with the development of increasingly effective invasive techniques for AF ablation, many unanswered questions remain regarding the pathogenic mechanism of the arrhythmia and its prevention methods. The development of AF is based on anatomical and functional alterations in the cardiomyocyte resulting from altered ionic fluxes and cardiomyocyte electrophysiology. Electric instability and electrical remodeling underlying the arrhythmia may result from oxidative stress, also caused by possible mitochondrial dysfunction. The role of mitochondrial dysfunction in the pathogenesis of AF is not yet fully elucidated; however, the reduction in AF burden after therapeutic interventions that improve mitochondrial fitness tends to support this concept. This selected review aims to summarize the mechanisms of mitochondrial dysfunction related to AF and the current pharmacological treatment options that target mitochondria to prevent or improve the outcome of AF.
Advanced Wearable Devices for Monitoring Sweat Biochemical Markers in Athletic Performance: A Comprehensive Review
Authors: Assalve Graziana , Lunetti Paola , Di Cagno Alessandra , De Luca Ernesto William , Aldegheri Stefano , Zara Vincenzo , Ferramosca Alessandra
Published: November 2024

Wearable technology has advanced significantly, offering real-time monitoring of athletes’ physiological parameters and optimizing training and recovery strategies. Recent developments focus on biosensor devices capable of monitoring biochemical parameters in addition to physiological ones. These devices employ noninvasive methods such as sweat analysis, which reveals critical biomarkers like glucose, lactate, electrolytes, pH, and cortisol. These biomarkers provide valuable insights into an athlete’s energy use, hydration status, muscle function, and stress levels. Current technologies utilize both electrochemical and colorimetric methods for sweat analysis, with electrochemical methods providing higher precision despite potential signal interference. Wearable devices such as epidermal patches, temporary tattoos, and fabric-based sensors are preferred for their flexibility and unobtrusive nature compared to more rigid conventional wearables. Such devices leverage advanced materials and transmit real-time data to computers, tablets, or smartphones. These data would aid coaches and sports medical personnel in monitoring athletes’ health, optimizing diets, and developing training plans to enhance performance and reduce injuries.
An Eye Tracker Study on the Understanding of Implicitness in French Elementary School Children
Authors: Bucci Maria Pia , Premeti Aikaterini , Godart-Wendling Béatrice
Published: November 2024

Background: The aim of this study is to use an eye tracker to compare the understanding of three forms of implicitness (i.e., presupposition, conversational implicatures, and irony) in 139 pupils from the first to the fifth year of elementary school. Methods: The child was invited to read short texts composed of a context about some characters and a target sentence conveying one of the three kinds of implicitness. After that, there was a comprehension yes/no question to check whether the child had understood the implicit content of the target sentence. At the same time eye, movements were recorded by a remote system (Pro Fusion by Tobii). The number of correct answers, the duration, and the number of fixations on the texts were measured. Results: We showed that children’s reading time is positively correlated with the accurate comprehension of implicitness, and that children similarly understand the three types of implicitness. Furthermore, the number and the duration of fixations depend both on the age of the children and on their good or poor understanding of the implicit contents. This fact is particularly noticeable for children in the first-grade class, for whom fixations are significantly longer and more frequent when they correctly understand sentences containing implicitness. Conclusion: These results argue in favor of the possibility of teaching the comprehension of some types of implicitness (presupposition, implicature, and irony) from an early age.
Investigating the Effectiveness of a Virtual-Reality-Based Mindfulness Intervention on Internet Gaming Disorder
Authors: Tvrtković-Hasandić Selma , Ünal-Aydın Pınar
Published: November 2024

Novel treatment approaches for Internet Gaming Disorder (IGD) include the use of mindfulness and technology-based interventions. Mindfulness has been shown as a protective factor against IGD, but the treatment dropout rates are high due to long sessions and treatment duration. Pathological gamers show approach bias towards technological gadgets, and the inclusion of Virtual Reality has been effective in IGD treatment. Due to the effectiveness of mindfulness and the attractiveness of VR, a combined intervention could decrease treatment time and willingness for treatment. Therefore, the aim of this study was to examine the effectiveness of a brief VR-based mindfulness intervention on IGD symptomatology. Nine participants meeting the IGD symptom criteria, ten recreational game users, and eight healthy controls without a gaming history participated in the study. The intervention consisted of four weekly 20-min-long Attentional Focus Mindfulness sessions. The results indicate a significant reduction in IGD symptoms and weekend gaming time in the treatment group. Despite the small sample size in the treatment group (n = 9) and lack of randomization, the findings constitute a valuable starting point. As a cost- and time-effective intervention, this approach could reduce dropout rates and increase treatment adherence, especially in younger gamers. Additional studies with a larger sample size, randomization, and a longitudinal approach are needed to further validate the found results.
Field Measurement and Numerical Simulation of Sound Insulation Characteristics of Buildings Along Elevated Urban Rail Lines
Authors: Wang Teng , He Wei , Wang Dongyang , Chen Jialiang
Published: November 2024

The noise pollution issue along elevated urban rail transit lines has attracted considerable attention; however, research on the sound insulation characteristics of buildings during operational train noise remains limited. In this study, a field testing campaign was conducted in a building featuring facades constructed from aerated concrete blocks embedded with single-layer glass sliding windows along an elevated rail transit line. The sound insulation characteristics of the building were obtained based on measured data. By neglecting the influence of lateral sound transmission, a window-wall assembly model was proposed for simulating the building’s sound insulation capability. To ensure the accuracy of the prediction results, initial simulations were first performed on individual elements and compared against the experimental sound insulation curves to identify key parameters. Subsequently, simulations of the window-wall assembly model were carried out and compared with test data to determine the acoustic boundary treatment. The results showed that the amount of sound insulation measured in the buildings ranged from 11.16 dB (A) to 19.85 dB (A) during train passage, exhibiting a notable dip in sound insulation within the frequency range of 80 Hz to 100 Hz. Conversely, the predicted sound insulation of 26.38 dB was much higher, also showing a significant dip at around 100 Hz. The simulated values aligned closely with the measured values below 500 Hz; however, discrepancies were observed in mid-to-high frequency ranges above this threshold. To this end, further simulations were performed on a window-wall assembly model incorporating air gaps to take into account air leakage effects. The results indicated that the presence of air gaps considerably diminished high-frequency sound insulation; when accounting for window air leakage effects, the simulated results approached closer alignment with the measured ones.
Harnessing Disruptive Innovation: A Conceptual Model for SME Growth and Adaptation
Authors: Smuts Hanlie , Weilbach Lizette , Padachi Kesseven , Boolaky Aleesha , Mauree-Narrainen Diroubinee , Ramphul Needesh , Chittoo Hemant
Published: November 2024

In the context of sustaining innovation, small and medium enterprises (SMEs) strive to enhance their market position through product improvements. However, globalization and rapid technological advancements pose significant challenges, urging SMEs to integrate innovative capabilities into their business models. Effective SME business model innovation, fueled by customer insights, process efficiency, and technology application, can promote development and unlock additional value-creation resources. Despite this, SMEs encounter difficulties in capitalizing on disruptive innovation due to the competitive, technology-driven, and volatile global market. This study aimed to define a comprehensive conceptual model of disruptive innovation specifically tailored for SMEs. Through an automated content analysis of relevant literature, 13 themes and 82 concepts were identified and categorized into four strategic alignment domains. These domains provide a framework for operationalizing the findings and constructing a conceptual model of disruptive innovation. Utilizing this conceptual model as a checklist can assist SMEs in turning disruption into opportunity, thereby supporting their adaptation and growth in an increasingly competitive landscape.
Heterogeneous Surface CD79b Expression in Aggressive B-Cell Lymphomas Assessed by Flow Cytometry on Lymph Node Biopsies
Authors: Maiolo Elena , Bellesi Silvia , Campana Fabrizia , Iacovelli Camilla , Malafronte Rosalia , Schiaffini Gabriele , Alma Eleonora , Bellisario Flaminia , Viscovo Marcello , D’Innocenzo Simone , Toscano Alessia , D’Alò Francesco , De Stefano Valerio , Larocca Luigi Maria , Hohaus Stefan
Published: November 2024

Background: CD79b is a B-cell-specific antigen that is crucial to the B-cell receptor and is considered a key target for treatment in aggressive B-cell lymphomas. Methods: While immunohistochemical studies have shown widespread expression of CD79b in mature B-cell-derived lymphomas, flow cytometry allows for precise measurement and differentiation between surface and intracellular localization. Results: In our comparative analysis, we discovered that CD79b expression percentages and mean fluorescence intensity (MFI) were lower in a group of 127 cases of aggressive B-cell lymphomas compared to a control group of benign reactive hyperplasia. We also observed significant variability in the surface expression of CD79b among lymphoma cases, with 18% showing predominantly intracellular positivity. There was a strong correlation between the surface expression of CD79b and clonal light chains. Notably, primary mediastinal B-cell lymphomas exhibited significantly lower surface CD79b expression compared to other lymphoma subtypes (median 0.8% IQR 0–48.5 vs. 80% IQR 24–97, p = 0.0005). Furthermore, patients over 60 years old and those with a higher Revised International Prognostic Index (R-IPI) had significantly higher CD79b expression, both of which are associated with a significant benefit from adding an anti-CD79b drug conjugate to first-line chemotherapy in diffuse large B-cell lymphomas. Conclusions: In conclusion, the quantitative flow cytometric analysis of CD79b surface expression in aggressive B-cell lymphomas provides clinically relevant information, highlighting its potential usefulness in guiding therapeutic decisions.
Detection of Mismatch Repair Deficiency in Endometrial Cancer: Assessment of IHC, Fragment Length Analysis, and Amplicon Sequencing Based MSI Testing
Authors: Sowter Peter , Gallon Richard , Hayes Christine , Phelps Rachel , Borthwick Gillian , Prior Shaun , Combe Jenny , Buist Holly , Pearlman Rachel , Hampel Heather , Goodfellow Paul , Evans D. Gareth , Crosbie Emma J. , Ryan Neil , Burn John , Santibanez-Koref Mauro , Jackson Michael S.
Published: November 2024

Background/Objectives: Mismatch repair (MMR) deficiency can be indicative of Lynch syndrome (LS) and guide treatment with immune checkpoint inhibitors. Colorectal cancers (CRCs) and endometrial cancers (ECs) are routinely screened to identify LS, primarily using immunohistochemistry (IHC) or microsatellite instability (MSI) testing, but concordance between these methods is variable in ECs. Here, we investigate this variability in 361 ECs from the Ohio OCCPI/OPTEC (n = 196) and Manchester PETALS (n = 165) trials, where concordance between assays differed significantly. Methods: Samples were re-tested using the amplicon-sequencing-based Newcastle MSI assay (NCL_MSI), and analysed with respect to existing IHC, MSI and MLH1 promoter hypermethylation data. Results: NCL_MSI showed consistency with the Ohio results (94% and 97% concordance with IHC and original MSI assays, respectively) and increased concordance within the Manchester cohort from 78% to 86% (MSI) and 84% (IHC). Among discordant Manchester samples, NCL_MSI was significantly associated with MLH1 promoter methylation status (p = 0.0028) and had the highest concordance with methylation, (62/69 samples, 90%), indicating utility as a screening tool in this tumour type. However, tumours with germline MSH6 defects were only detected efficiently with IHC; seven out of eight LS tumours classified as MSS by either MSI assay had isolated MSH6 loss, compared to four out of twelve classified as MSI-H by both (p = 0.028). Furthermore, reduced MSI signal was observed in tumours with isolated MSH6 loss (p = 0.009 Ohio, p = 6.2 × 10−5 Manchester) and in both ECs and CRCs with germline defects, although this only reached significance in CRCs (p = 0.002). Conclusions: These results provide further evidence that ECs with MSH6 loss in particular and LS tumours in general have an attenuated MSI signal, providing support for current guidelines specifically recommending IHC for LS detection and immune checkpoint therapy assessment in EC.
Inflammation and Related Signaling Pathways in Acute Myeloid Leukemia
Authors: Naji Nour Sabiha , Sathish Mrudula , Karantanos Theodoros
Published: November 2024

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, and inflammatory signaling is involved in its pathogenesis. Cytokines exert a robust effect on the progression of AML and affect survival outcomes. The dysregulation in the cytokine network may foster a pro-tumorigenic microenvironment, increasing leukemic cell proliferation, decreasing survival and driving drug resistance. The dominance of pro-inflammatory mediators such as IL-11β, TNF-α and IL-6 over anti-inflammatory mediators such as TGF-β and IL-10 has been implicated in tumor progression. Additionally, inflammatory cytokines have favored certain populations of hematopoietic stem and progenitor cells with mutated clonal hematopoiesis genes. This article summarizes current knowledge about inflammatory cytokines and signaling pathways in AML, their modes of action and the implications for immune tolerance and clonal hematopoiesis, with the aim of finding potential therapeutic interventions to improve clinical outcomes in AML patients.